ResearchPad - case-reports-in-secretory-pituitary-pathologies-their-treatments-and-outcomes https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SAT-278 Vaginal Cabergoline: A Simple Solution to a Challenging Problem]]> https://www.researchpad.co/article/elastic_article_8802 Introduction: Prolactinomas is a common endocrine disorder that can be associated with significant morbidity. Generally, prolactinomas are more responsive to pharmacologic treatment than any other types of pituitary adenoma. Dopamine agonists (DA), including cabergoline and bromocriptine, are the first line of treatment in all sizes of prolactinomas and they decrease both the secretion and size of these adenomas. However, treatment remains challenging for patients who are intolerance to those medications. Case: We report a 32-year-old Hispanic woman who presented with secondary amenorrhea, she was found to have hyperprolactinemia of 1496 mcg/L. MRI of the brain showed a pituitary adenoma measuring 2.7 cm with sella turcica invasion and mass effect on the optic chiasma. She failed the lowest doses of oral cabergoline and bromocriptine and underwent TSS and gamma knife radiosurgery. Given her persistent symptoms (marked depression, insomnia, fatigue, short-term memory loss, and lack of concentration along with constipation) and elevation of prolactin, she was started on low dose vaginal cabergoline leading to a marked improvement of her symptoms and a steady decrease in serum prolactin. Discussion: Despite the availability of DA as a first-line treatment of Prolactinoma, treatment remains challenging, given the commonly reported side effects for all DA. Cabergoline is oftentimes the treatment of choice due to efficacy and favorable side-effect profile. However, intolerance to those medications can lead to discontinuation of therapy and increase morbidity. Other strategies, including transsphenoidal surgery (TSS) or radiation therapy, have been considered for the minority of patients whose adenomas are resistant to DA or who cannot tolerate these drugs. Interestingly, tolerance to DA can be improved by administering the drug intravaginally, which can have similar efficacy to the oral route and a more favorable side-effect profile. However, only a few studies assessed the effectiveness and tolerance of vaginal DAs in hyperprolactinemic patients intolerant to oral medications, little evidence supports the use of intravaginal DA to improve drug tolerance, and further studies are necessary to determine the safety and efficacy of vaginal cabergoline.

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<![CDATA[SAT-265 An Asynchronous Double Growth Hormone Secreting Pituitary Adenoma as a Cause of Rapid Tumor Regrowth After Initially Successful Surgery]]> https://www.researchpad.co/article/elastic_article_8762 Background. Double pituitary adenomas are a rare entity, which requires clinical attention and a careful follow-up. Case report. A 37-year-old man presented with left-sided painful gynecomastia. He denied typical symptoms of excessive growth hormone (GH) secretion and did not show any acromegalic features. Due to low testosterone and LH levels with mild hyperprolactinaemia, the patient was referred to pituitary MR, which revealed an 11x13 mm right-sided sellar tumor. An increased IGF-1 was noted subsequently (1482 ng/mL; N 109-284 ng/mL), together with the lack of GH suppression in OGTT. Transphenoidal resection of pituitary tumor performed in 2012 led to biochemical (IGF-1 260 ng/mL, GH 0.08 ng/mL) and radiological remission of the disease. A histopathology report revealed a densely granulated somatotropic pituitary adenoma with mild nuclear atypia, expressing somatostatin receptors [sstr2A (+), sstr5 (+/-)]. Due to gradually increasing IGF-1 levels (with low, although rising, GH values ranging from 0.07 to 0.92 ng/mL) in subsequent years, OGTT was repeated in 2015, showing appropriate GH suppression. In 2016, however, acromegaly recurrence was confirmed both biochemically (increasingly high IGF-1 - 664 ng/mL - and unsuppressed post-OGTT growth hormone) and in MR imaging. The patient was reoperated in June 2017. The second histopathology reported an oncocytic somatotropic acidophil stem cell pituitary adenoma with Ki-67 >3% and mitotic figures. Subsequent anterior pituitary lobe insufficiency (adrenal, thyroid and gonadal axis) was found and adequately treated. Complete tumor removal was confirmed by MR performed three months after repeated surgery, as well as a low GH level (0.97 ng/mL), although accompanied by borderline IGF-1 values (277 ng/mL). Eighteen months after surgery, the recurrence of acromegaly was again confirmed, with adenoma regrowth and increased GH (2.31 ng/mL) and IGF-1 (474 ng/mL) levels. Octreotide LAR was started (despite retina wrinkling which was observed when lanreotide was administered before the first surgery), which led to a normalization of GH (0.96 ng/mL) and IGF-1 levels (152 ng/mL), as well as partial pituitary tumor regression after six months therapy. Conclusion. In a case of GH-secreting pituitary adenoma recurrence after apparent successful surgery, a double pituitary tumor with more aggressive histology should be considered.

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<![CDATA[SAT-251 New Diagnosis of Acromegaly with DKA as Initial Presentation]]> https://www.researchpad.co/article/elastic_article_8744 Background: While diabetes mellitus from growth hormone related insulin resistance is not uncommon in GH secreting tumors, initial presentation with diabetic ketoacidosis is rare.

Clinical Case: 31 YO male with no significant past medical history presented with c/o fatigue, 40 lb weight loss, polyuria, polydipsia. Clinical features of acromegaly with frontal bossing, protruding jaw, large hands and feet, thick spade like fingers, hammer toes, high arches and thickened fat pads on both feet were noted. Initial labs were consistent with DKA with anion of 31 mmol/L (0-20), blood glucose 241 mg/dl, bicarb 12 mmol/L (22-29), serum betahydroxy butyrate > 8 mmol/L (0-0.29), urine positive for glucose, ketones, protein. Patient was initially treated with IV insulin per DKA protocol, transitioned to subcutaneous insulin.

MRI brain showed 2.1x1.3x2.1 cm pituitary macro adenoma. Labs showed elevated IGF1 LC/MS, S 1094 ng/ml (54-310), IGFBP3 14 mcg/ml (3.5-7), Z score IGF MS Mayo > 3 (-2 to +2), normal FSH 7.1 m unit/ml (1.5-12.4), normal LH 3.4 m unit/ml (1.7-8.6), normal prolactin 6 ng/ml (4-15), normal ACTH 10 pg/ml, cortisol 13.4 mcg/dl, low total testosterone 48.2 ng/dl (193-836), normal free testosterone 7.92 ng/dl (4.85-19), normal TSH 1.55 mc unit/ml (0.27-4.2) and free T4 1.17 ng/dl (0.93-1.7). The patient was discharged home on 120+ units of total daily dose of insulin, after initial hospital admission.

He underwent trans sphenoidal resection of pituitary macro adenoma one month after his initial presentation. Surgical pathology confirmed growth hormone producing adenoma. He was successfully weaned off from insulin in one month following surgery.

Conclusion: DKA is an unusual initial presentation of growth hormone producing tumors. As more cases are being reported it is important to be vigilant to look for DKA presentation in these patients and adjust/wean patients insulin once the growth hormone producing tumor is treated either with surgery or medications.

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<![CDATA[SAT-267 Pregnancy in Acromegaly: Report of Five Cases]]> https://www.researchpad.co/article/elastic_article_8728 Introduction: In acromegaly, there are changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin, hormones very important in pregnancy as well. Despite novel treatments, pregnancy in acromegaly is uncommon, remaining a challenge for clinicians.

We report seven pregnancies in five women with acromegaly.

Clinical Cases: Five acromegalic patients (17 – 35 years-old) underwent seven pregnancies. All patients had macroadenoma: four were submitted to non-curative neurosurgery and two of them had gamma-knife radiosurgery. One patient had medical treatment prior to curative transsphenoidal surgery (TSS).

One patient being treated with estroprogestative for hypogonadism had a spontaneous pregnancy; three others had pregnancy just before biochemical diagnosis of acromegaly, one of them had also a spontaneous abortion and another successful pregnancy during treatment with somatostatin receptor ligand (SRL); the last patient become pregnant during treatment with SRL, prior to TSS.

Monitoring was made with IGF-1, GH (assay with no distinction of pituitary GH versus placental GH), prolactin (PRL) and visual field; pituitary imaging was performed after pregnancies in all.

All women conceived naturally, two being on treatment with SRL (discontinued after confirmation of pregnancy). No treatment for acromegaly was administered before delivery. All patients had physiologic pregnancies, delivered full-term healthy babies, no malformations or metabolic disruptions; one did not breast-feed; another one had a spontaneous abortion 2 days after confirmation of pregnancy.

No patient developed either hypertension, pre-eclampsia or gestational diabetes.

In three cases, the clinical suspicion of acromegaly had risen during pregnancy and the diagnosis was made 1 year after delivery. The one with three pregnancies had controlled secretion of GH on Lanreotide and GH and IGF-1 levels remained stable during pregnancy.

The woman with gonadotroph deficiency after TSS and GK and substitutive therapy had a decrease in IGF-1 during pregnancy (45 %), which after delivery returned pathologically to before pregnancy values; GH levels remained stable.

The last patient, who became pregnant with uncontrolled acromegaly on Pasireotide, had increased, but stable GH and IGF-1 (2 X upper limit of normal) before, during and after pregnancy. TSS performed 3 years after delivery cured the disease.

Conclusion: From our experience, patients with acromegaly may have normal babies, even in patients with uncontrolled hypersecretion and lack of medical treatment during pregnancy. The consensus is, however, that there is no indication to use medication to control GH hypersecretion or tumor size in acromegaly patients during pregnancy (1).

Reference: (1) Muhammad A, Neggers SJ, van der Lely AJ. Pregnancy andacromegaly. Pituitary. 2017;20(1):179–184. doi:10.1007/s11102-016-0740-3

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<![CDATA[SAT-256 The Ever Confusing Cushing’s Work Up: Is It Real? Is It Pseudo Cushing’s’? Or Could It Be Factitious]]> https://www.researchpad.co/article/elastic_article_8692 Case Presentation:

A 50 year old female initially presented with progressive weight gain and mood swings. She had normal 24 h urine cortisol, but an elevated midnight serum cortisol. She underwent transphenoidal surgery for a presumed ACTH-dependent Cushing’s disease. Pathology was not supportive of a pituitary adenoma, showing adenohypophyseal tissue with focal expansion of the acini. The surgery was complicated by hypothyroidism and growth hormone deficiency. She was able to weaned off of the steroids after a few months. She had recurrence of her initial symptoms, she was found to have elevated late evening and morning cortisol levels. She underwent a bilateral adrenelactomy for “recurrence of the cyclical Cushing’s symptoms.” She was started on HC replacement; 10 mg AM and 2.5 mg PM, florinef 0.05 mg daily. She slowly lowered the hydrocortisone dose, and as a result lost 120 lbs.

Three years later she presented with fatigued and gaining weight, by that time she was on Hydrocortisone 3.75 mg AM, 1.25 mg evening, and fludrocortisone 0.1 mg/day. ACTH was 355 (6–48 pg/ml), serum cortisol 10 (8–19 ug/dl) on Hydrocortisone and < 1.0 ug/dl off cortisone. The 24 h urine free cortisol < 1.0 (10–24 ug/34h), and 17 OH- corticosteroids < 4.8(4–14 mg/dl). A possible adrenal remnant was seen on abdominal CT, surgically removed of the lesion showed a lipoma.

She was referred to Neurosurgery for a second pituitary surgery for the concern Cushing’s recurrence. A pituitary MRI revealed a small potential microadenoma. The small dose of hydrocortisone was held for 48 h and an 8 AM test dose: Serum cortisol < 1.20 mcg/dl (3–18), ACTH 1,077 pg/ml (5–72), 24 h urine cortisol < 1.5 mcg/24h (3.5–45), 24 h urine cortisone 10 mcg/24h (17–129), and two midnight salivary cortisol were 128 and 265 ng/dl (< 100 ng/dl). There was a concern raised by the laboratory for a contaminated salivary sample, as the salivary cortisol to cortisone ratio was concerning for contamination with exogenous steroid (1)

Discussion:

Work up for Cushing’s syndrome can be very confusing and frustrating at times for the patient and their physicians. Doing a meticulous work up is necessary to reach an accurate conclusion. Misdiagnosing Cushing’s can lead to a cascade of mistreatment with serious consequences. The case presented highlights the challenges encountered in taking care of such patients. It is necessary to understand the pre-testing probability to reach a precise conclusion. Factitious disorder or sample contamination can be yet another challenge in the differential diagnosis of Cushing’s work up.

(1)

Raff H Measurement of Late-Night, Salivary Cortisol and Cortisone by LC-MS/MS to Assess Preanalytical Sample Contamination with Topical Hydrocortisone. Clinical Chemistry 58:5 (2012)

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<![CDATA[SAT-LB46 Depression as an Atypical Presentation of Cushing’s Disease]]> https://www.researchpad.co/article/elastic_article_8562 Introduction: Cushing’s disease is an abnormal secretion of ACTH from the pituitary that causes an increase in cortisol production from the adrenal glands. Resultant manifestations from this excess in cortisol include multiple metabolic as well as psychiatric disturbances which can lead to significant morbidity and mortality.

Case: The patient is a 29 year old woman who presented with fatigue, decreased energy, poor memory and insomnia for 3 months. She noted irregular menses for 4 months. She was referred from her primary doctor for elevated salivary cortisol and DHEA levels. Evaluation revealed BP: 104/76, HR 78, RR 12, BMI 22.7. She was a thin woman without striae, moon face, buffalo hump or bruising. 24 hour urine free cortisol was 90.3 mcg/24hr. One mg dexamethasone suppression test resulted in an AM cortisol of 17.6 ug/dL and ACTH 25 pg/mL. An 8 mg dexamethasone suppression test showed a cortisol level of 1.2 ug/dL with an ACTH <5 pg/mL. The combined results were suggestive of Cushing’s disease. The patient went for MRI of the pituitary which showed a 4 mm hypoenhancing region on the right side of the gland suspicious for a microadenoma. The patient was followed closely and continued to report fatigue and insomnia. Inferior petrosal sinus sampling was performed. Venous blood sampling of ACTH from the periphery at 0 min, 5 min and 15 min were: <5 pg/mL, <5 pg/mL, and <5 pg/mL respectively. On the right at 0 min, 1 min, 5 min, 15 min ACTH levels were: 12 pg/mL, 14 pg/mL, 16 pg/mL, 14 pg/mL. On the left at 5 min and 15 min ACTH measured 8 pg/mL and 7 pg/mL. These findings confirmed the suspicion of a right-sided ACTH-secreting pituitary adenoma. She was referred to a neurosurgeon to evaluate for resection of the adenoma. Due to the ongoing symptoms, the neurosurgical removal of the lesion was expedited and scheduled within several weeks. While awaiting removal the patient sadly took her own life.

Conclusion: Aside from the more commonly associated metabolic manifestations of elevated cortisol levels, psychiatric symptoms can be the initial complaint of patients with Cushing’s disease. Symptoms can include fatigue, depressive symptoms, insomnia, and sleep dysregulation. Currently the Endocrine Society Guideline for Cushing’s syndrome does not have any specific recommendations regarding depression screening. Psychiatric complications are a known manifestation of Cushing’s disease. Close follow up and urgent psychiatric referral with the onset of signs of depression or anxiety should be included as part of Cushing’s disease evaluation. Symptoms of mental health disturbances may be subtle and thus all patients with Cushing’s disease should be screened and monitored for underlying psychiatric illnesses.

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152600/pdf/JMedLife-09-12.pdf

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<![CDATA[SAT-258 Surprising Transformation of a Microprolactinoma to a Macroprolactinoma]]> https://www.researchpad.co/article/elastic_article_7180 Background: Microprolactinomas are typically benign tumors that rarely become macroprolactinomas. We present a rare case of a microprolactinoma that, after discontinuation of dopamine agonist (DA) therapy, transformed into a macroprolactinoma over a period of 6 years.Clinical Case: A 16-year-old woman initially presented for evaluation of galactorrhea without menstrual irregularities and was found to have elevated prolactin (68 ng/ml, normal range: 0-20), and a 4 mm pituitary microadenoma on MRI imaging. The patient was otherwise asymptomatic and other pituitary hormone levels were normal. She was treated with DA therapy (cabergoline 0.50 mg/week) which normalized her PRL level and improved but did not completely resolve the galactorrhea. She was then lost to follow up for 6 years. During that time, she discontinued cabergoline, but was still able to conceive, delivering a healthy baby after 2 years and breastfed briefly. She re-presented to her gynecologist 4 years after delivery for galactorrhea and secondary amenorrhea, both persistent since childbirth. Re-evaluation at that time revealed a much higher PRL level (432 ng/ml) and significant interval growth of the previous microadenoma to a 2.6 cm macroadenoma, now with extension into the left cavernous sinus, suprasellar cistern, with mass effect on the optic chiasm. The patient was retreated with cabergoline up to 3 mg/week, with a near-normal PRL level being achieved at 9 months (28 ng/ml). Repeat MRI revealed modest decrease of the adenoma to 2.4 cm. Galactorrhea resolved with reduction in PRL. However, amenorrhea persisted. Estradiol (30 pg/mL, 19-357 pg/mL) was low normal with normal withdrawal bleeding to medroxyprogesterone (MPA) challenge indicating reasonable estrogenization. She was treated with MPA to achieve regular cyclic bleeding every 3 months. Conclusion: This is an unusual case demonstrating significant growth of a microprolactinoma, which is typically a stable/indolent neoplasm, to a macroprolactinoma with invasive features. Previous studies of untreated microprolactinomas have shown that they undergo only subtle to minimal growth over 3 to 6 years and none transformed to a macroprolactinoma despite significant rises in PRL levels. In this clinical case, given the 6 intervening years that had elapsed in between MRIs, we cannot determine whether this represented moderate, progressive growth during that period after the discontinuation of DA therapy or whether the tumor had grown during pregnancy with its known stimulatory effects from hyperestrogenemia. The patient will require close follow-up to ensure ongoing shrinkage or at least stability of the adenoma and ongoing control of her hyperprolactinemia.References:1. Fertility and sterility39, 753-760 (1983). 2. Dietemann, J.L et al. Neuroradiology25, 133-138 (1983). 3. Garcia, M.M et al. Journal of endocrinological investigation18, 450-455 (1995).

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<![CDATA[SAT-269 A Rare Case of Functioning Gonadotroph Producing Pituitary Macroadenoma in Teenage Male]]> https://www.researchpad.co/article/elastic_article_6915 Background: Unlike nonfunctioning gonadotroph pituitary adenomas, functioning gonadotroph pituitary adenomas (FGA) are an uncommon type of pituitary tumors that secrete biologically active gonadotropins (LH, FSH, or both).

Clinical Case: A 23-year-old man with no previous medical history presented to the emergency department with three months history of progressive decreased vision and decreased libido. He denied headache, seizure, erectile dysfunction, or weakness. On physical examination, his visual acuity was significantly reduced on the right eye and was only able to perceive light. He had a visual field narrowing on the left eye. Gynecomastia was noted bilaterally and testicles were found to be enlarged (Orchidometer >25 mL). Complete blood count was significant for hemoglobin of 19.2 g/dL (N, 13.7-17.5 g/dL), and hematocrit of 57.0% (N, 40.1-51.0%). Pituitary function tests were as follow: FSH >200.0 mIU/mL (N, 1.5-12.4 mIU/mL), LH 17.0 mIU/mL (N, 1.7-8.6 mIU/mL), total testosterone 41.3 nmol/L (N, 8.6-29.0 nmol/L), free testosterone 1.263 nmol/L (N, 0.148-0.718 nmol/L), and bioavailable testosterone 29.609 (N, 2.110-8.920 nmol/L). Prolactin, TSH, GH, and ACTH were all within the normal range. Magnetic resonance imaging (MRI) showed a sellar mass involving the planum sphenoidal measuring 5.8 x 5.2 x 5.6 cm with optic chiasm displaced superiorly, in addition, subfalcine herniation with mild hydrocephalus was also noted. The patient underwent orbitozygomatic approach resection of the pituitary tumor. Histological examination was consistent with a pituitary adenoma. Cells stained positive for transcription factor steroidogenic factor 1 (SF 1), FSH, LH, and alpha-subunit consistent with a gonadotroph adenoma. They were negative for transcription factor Pit 1 stain and the remaining pituitary hormones including ACTH, GH, prolactin, and TSH stain. Postsurgical hormone assessment showed a significant decline in FSH and LH to 2.3 and 0.4 mIU/mL, respectively and testosterone level decreased to < 0.087 nmol/L on postoperative day 18. The patient’s vision improved postoperatively prior to discharge but he lost follow up thereafter.

Conclusion: Most patients with functioning gonadotroph pituitary adenoma present with large tumors that are detected based on the occurrence of symptoms of compression that result from the enlarging sellar mass. Most patients, particularly men and postmenopausal women, do not develop symptoms of hormone excess and the lack of symptomatology results in delay in diagnosis. Our patients presented with significant polycythemia which resulted from excess testosterone and could have prompted earlier tumor detection if he had presented in an earlier stage. The incidence of polycythemia in male patients with functioning gonadotroph pituitary adenoma has previously been described in the literature in a few case reports.

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<![CDATA[SAT-279 Crooke’s Cell Adenoma- an Aggressive Form of Cushing’s Disease]]> https://www.researchpad.co/article/elastic_article_6857 Introduction: Cushing’s disease is a condition of cortisol overproduction caused by an ACTH-producing tumor. Corticotroph cells surrounding an ACTH-producing tumor usually undergo Crooke’s hyaline change, where cytokeratin filaments accumulate in the cytoplasm in response to glucocorticoid excess. These changes are thought to be a mechanism of feedback inhibition and thus facilitate a suppression of ACTH. However, in a subtype of ACTH-secreting tumors known as Crooke’s cell adenomas (CCA), the ACTH-producing cells also undergo these hyaline changes. This would be expected to suppress hormone secretion but these cells are still able to release significant amounts of ACTH.

Case presentation: A 32-year-old woman presented to the hospital after an episode of syncope. On head MRI, she was found to have a 2 cm sellar mass with optic chiasm compression. Labs showed low TSH, free FT4, T3, FSH, and LH. She was also pre-diabetic with an HgbA1c of 6.2%. Her baseline cortisol of 20.6 µg/dL did not suppress after 1 mg of dexamethasone. After receiving 4 mg of dexamethasone, her cortisol suppressed to 5.2 µg/dL. She was diagnosed with hypopituitarism except for cortisol and a likely ACTH-producing pituitary macroadenoma. She completed a transsphenoidal pituitary resection and pathology revealed Crooke’s hyaline changes with immunohistochemical stains positive for ACTH. The immunostain for the proliferation marker Ki67 showed a relatively low proliferation index. Her course was complicated by diabetes insipidus. She was ultimately discharged on 20 mg hydrocortisone each morning, 10 mg hydrocortisone each afternoon, desmopressin 0.05 µg daily, and levothyroxine 125 µg daily. Two weeks later, the patient was sent to the emergency room by her endocrinologist for hyperglycemia up to 288 mg/dL. She was also found to be newly diabetic with an HgbA1c of 6.5%. A fasting morning cortisol was collected during her admission and showed a cortisol level of <1.0 µg/dL, proving she was cured of Cushing’s disease. However, she will need close endocrinology follow up and MRI imaging of her pituitary for this aggressive type of pituitary adenoma.

Discussion: We have come across an interesting case of a young woman who presented for syncope and was found to have a pituitary macroadenoma with pathology consistent with CCA. This type of ACTH-producing tumor is known for aggressive patterns including high rates of recurrence with rates of up to 60% reported in literature, persistent disease after surgery, malignant transformation, and metastases. Despite presentation and symptoms similar to those of other ACTH-producing adenomas, the dangerous pattern of Crooke’s cell adenomas necessitate long-term follow-up in affected patients.

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<![CDATA[SAT-250 A Case of Late Recurrent Cushing’s Disease Presenting with Proximal Myopathy]]> https://www.researchpad.co/article/elastic_article_6849 Patients with Cushing’s disease (CD) present with a variety of symptoms and comorbidities including central obesity, hypertension, hyperglycemia, fatigue, weakness, insomnia and mood changes. Proximal myopathy is one of the classical signs of hypercortisolism and patients typically report difficulty rising from a seated position or climbing stairs. Due to variability in clinical presentation, with some patients showing subtle or few symptoms, the diagnosis of CD can be delayed. We describe a patient with late recurrent CD whose primary symptom was proximal myopathy. A 63 yr. old man presented to our clinic with complaints of progressive muscle weakness and fatigue. He had been successfully treated for CD at age 35 with transsphenoidal pituitary adenomectomy. He had been on hormonal replacement therapy for panhypopituitarism since surgery including levothyroxine, testosterone and glucocorticoids. He noted progressive weakness for several years prior to presentation in our clinic. Earlier evaluations revealed vitamin B12 and vitamin D deficiency, but supplementation did not lead to significant symptom improvement. He suffered two episodes of unprovoked deep venous thrombosis with pulmonary embolism and developed a left biceps tear that required hospital admission. During admission, his muscle weakness was exacerbated by immobility and he was subsequently referred to endocrinology for consideration of steroid induced myopathy. He had been on physiologic glucocorticoid replacement since diagnosed with panhypopituitarism. At the time of our evaluation, he was able to ambulate with a walker, but was unable to climb stairs, drive a car and required assistance with activities of daily living. His only other symptoms were fatigue and insomnia. Laboratory testing after holding prednisone revealed: morning cortisol 31.7 mcg/dl (reference interval [RI], 4.0-22.0), ACTH 128 pg/mL (RI 6 - 50), FSH <0.7 mIU/mL (RI 1.6 - 8.0), LH <0.2 mIU/mL (RI 1.6 - 15.2), testosterone 85 ng/dL (RI 250 - 827), IGF-1 55 ng/mL (RI 41 - 279), prolactin 4.9 ng/mL (RI 2.0 - 18.0), TSH 0.01 mIU/L (RI 0.40 - 4.50), free T4 1.5 ng/dL (RI 0.8 - 1.8), HbA1c 6.8% (RI <5.7%). Prednisone was discontinued and hypercortisolism was confirmed by 1 mg overnight dexamethasone (dex) suppression test (Cortisol 32.4 mcg/dL, dex 517 ng/dL, RI 180-550 ng/dL) and elevated 24 h urine free cortisol 315.4 mcg/24h (RI 4.0 - 50.0). 8 mg DST showed mild cortisol suppression (Cortisol 21.2 mcg/dL, dex >1000 ng/dl). MRI confirmed recurrent tumor (1.2 x 0.8 x 1.3 cm) extending into the right cavernous sinus and the patient underwent repeat transsphenoidal tumor resection. Pathology confirmed ACTH adenoma. Our case report highlights that patients with CD can have late recurrences and require long term monitoring for return of hypercortisolism, even in cases of prior panhypopituitarism.

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<![CDATA[SAT-LB52 A Case of Cushing’s Syndrome in a Patient With Addison’s Disease]]> https://www.researchpad.co/article/elastic_article_6587 This is a case of a 56-year-old female with history of Addison’s disease, T1DM, hypothyroidism and Asthma. She was diagnosed with Addison’s disease after multiple hospital visits consistent with adrenal crises (Fatigue, weakness, salt craving, abdominal pain, hypotension, hyperpigmentation and hyponatremia). Multiple abdominal images including CT abdomen did not reveal any pathology. A random cortisol and ACTH were found to be abnormal at 0.5 and 3362, respectively. She was started on Hydrocortisone 10mg in the morning and 5mg in the evening. Her physical exam revealed diffuse hyperpigmentation including palmar creases and oral mucosa. There was no facial plethora or striae. She had no history of proximal myopathy, easy bruising, hypertension or osteoporosis. Upon follow up, exam revealed progressive worsening of her diffuse hyperpigmentation. A random cortisol and ACTH, without holding her Hydrocortisone, revealed 64.3 and >2000, respectively. Concern arose for the possibility for a pituitary corticotrophin adenoma or ectopic secretion of ACTH driving her hyperpigmentation. MRI showed the pituitary gland had normal appearances. As there is a positive correlation between basal plasma ACTH values and the size of the pituitary adenoma in patients with Cushing’s disease the differential of a pituitary corticotrophin adenoma was originally thought to be dropped lower on the list of differentials. Further workup was pursued with an 8mg Dexamethasone suppression test to take advantage of the fact that ACTH secretion by the pituitary adenomas in Cushing’s disease are only relatively resistant to negative feedback regulation by glucocorticoids while most ectopic ACTH production from non-pituitary tumors are completely resistant to feedback inhibition. ACTH levels went from >2000 down to 29 post 8mg Dexamethasone, which led to decreasing suspicion of an ectopic source of ACTH and further concern for a pituitary corticotrophin adenoma in addition to Addison’s disease. ACTH measurements are not widely used in documenting the adequacy of treatment of primary adrenocortical disease. The hormone is released in pulses, particularly in the early hours of the morning, and measurement of isolated samples is of limited value. Inappropriately normal to slightly elevated ACTH levels despite adequate glucocorticoid replacement in patient with adrenal insufficiency could be related to an altered pituitary sensitivity to cortisol suppression. Extremely elevated ACTH levels despite supra-physiological glucocorticoid replacement in a patient with Addison’s raises the question as to what is the source of ACTH?

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<![CDATA[SAT-275 Bitemporal Hemianopia as a Result of Cabergoline Therapy for Macroprolactinoma]]> https://www.researchpad.co/article/elastic_article_6402 Background: Cabergoline is first-line treatment for prolactin-secreting pituitary macroadenoma (prolactinoma). Side effects such as nausea, valvulopathy and neuropsychiatric symptoms are well recognized complications of its use. A rare complication is vision loss secondary to empty-sella syndrome. Clinical case: A 27-years old women was diagnosed in 2009 with macroprolactinoma with a prolactin level of 2,523.91ng/mL (normal 3.3-26.7ng/mL), during work up of frontal headaches, amenorrhea and infertility. The rest of her pituitary work up was normal. She was started on dopamine receptor agonist therapy with Cabergoline 0.25mg two times a week. Her headaches improved within a few month. The prolactin level normalized and MRI at 1 year after starting Cabergoline therapy showed significant decrease in pituitary adenoma to 3mm. She continued Cabergoline therapy for 3 years, after which time it was discontinued. For the next 6-8 years she was on and off Cabergoline therapy for mild elevation of prolactin and galactorrhea/headache symptoms, with improvement of symptoms on Cabergoline. However, nine years after diagnosis and Cabergoline treatment, she developed vision loss, characterized by bitemporal hemianopia. MRI showed partial empty sella with downward displacement of the optic chiasm. Cabergoline therapy was stopped with some improvement of visual symptoms on exam. Here latest prolactin level is at 134ng/ml. Surgical management with chiasmapexy is being explored. Conclusion: Vision loss secondary to optic nerve traction from chiasmal herniation in the setting of an empty sella can be a consequence of Cabergoline therapy. No predictors or risk factors are known for the development of this complication. Furthermore, no clear evidence is available of benefit from discontinuation/continuation of therapy. Novel surgical management with chiasmapexy is being explored as a solution to stabilize the optic chiasm and resolve visual symptoms without further complications.

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<![CDATA[SAT-LB45 Chronic Opioid Use as a Cause of Severe Hypothyroidism: A Case Report]]> https://www.researchpad.co/article/elastic_article_6302 Background: Hypogonadism and hypocortisolism are present in a sizeable proportion of chronic opioid users. (1) An association with hypothyroidism, however, has not been demonstrated.

Clinical Case: A 56-year old woman with chronic pain syndrome on opioids presented from a nursing home with decreased level of consciousness and was found to be hypotensive requiring ICU admission. Several weeks prior to her presentation, she was hospitalized for progressive weakness and was found to have evidence of panhypopituitarism: low TSH (0.209 uIU/mL, nl 0.400 – 4.200), low free T4 (0.76 ng/dL, nl 0.80 – 1.50), low LH (<0.12 mIU/mL, nl 10.9 – 58.6), low FSH (1.7 mIU/mL, nl 16.7 – 113.6), and abnormal ACTH stim test (ACTH 6.4 pg/mL, nl 7.2 – 63; cortisol 0-min 3.8 mcg/dL, nl 6.7 – 22.6; 60-min 13.10). She was discharged on levothyroxine 25 mcg daily and prednisone 7.5 mg daily. On admission, her exam was notable for symmetric, non-pitting edema of the lower extremities to the knees with peau d’orange appearance. Initial tests revealed profound hypothyroidism with low TSH (0.381 uIU/mL), low free T4 (0.60 ng/dL), undetectable total T4 (<0.9 mcg/dL, nl 5 – 12.2), and undetectable free T3 (<1.00 pg/mL, nl 2.5 – 3.9). Thyroglobulin and TPO antibodies were within normal limits. Thyroxine binding globulin was low (6 mcg/mL, nl 13 -39). Additional biochemical studies re-demonstrated panhypopituitarism with low LH (<0.12 mIU/mL) and FSH (0.9 mIU/mL). Cortisol was elevated (73.2 mcg/dL) as she had received hydrocortisone. Despite fluid resuscitation and use of vasopressors, her hypotension persisted and she remained in critical condition. She was treated as a case of myxedema coma and started on full replacement dose thyroid hormone with 120 mcg IV levothyroxine daily and liothyronine 5 mcg every 8 hours. Over the next several days, the patient’s hemodynamics and mental status improved dramatically. A contrast-enhanced pituitary-protocoled MRI was notable for a moderately flattened sella (pituitary 3.5 mm in height) and absence of usual T1 bright signal in the posterior lobe. A work-up for causes of panhypopituitarism was mostly unremarkable: low IgG 4 (0.82, neg <1.50), indeterminate quant gold, negative HIV, low serum iron (35 mcg/dL, nl 50 – 200). Urine toxicology was positive only for opioids, reflective of the patient’s chronic pain regimen consisting of MS-Contin 60 mg twice daily and methadone 10 mg twice daily.

Conclusion: This case demonstrates the potential for chronic opioid use to suppress the hypothalamic-pituitary-thyroid axis and highlights the importance of maintaining an index of suspicion for hypothyroidism in this population.

Reference: (1) de Vries, F., Bruin, M., Lobatto, DJ., Dekkers, OM., Schoones, JW., van Furth, WR., Pereira, AM., Karavitaki, N., Biermasz, NR., Najafabadi, AHZ. Opioids and their endocrine effects: A systematic review and meta-analysis. JCEM. 2019. Doi: 10.1210/clinem/dgz022

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<![CDATA[SAT-247 Use of Double Dopamine Agonists in Giant Prolactinomas: A Series of 6 Cases]]> https://www.researchpad.co/article/elastic_article_6136 Dopamine agonist monotherapy is first line therapy in giant prolactinomas even when visual field defect is present. The costlier cabergoline is often preferred over bromocriptine due to higher efficacy and tolerability profile. Described herein combined cabergoline and bromocriptine therapy in 6 cases of giant prolactinomas. Retrospective records review of 6 patients with giant prolactinoma (3 males: M1-M3, 3 females: F1-F3) in a single tertiary centre was performed. Mean age at diagnosis: 29 years (range 17-39). Mean duration of follow up: 7 years (range 3-11). Headache and visual field defect were the presenting symptoms in all cases. Basal prolactin concentration: 100000 to 468851 mIU/L (<300 for male, <600 for female). Three patients have hypopituitarism at presentation, one after surgery and one remained eupitary 5 years after diagnosis. One developed late onset hypopituitarism 4 years after normalisation of prolactin levels. Three patients underwent debulking at presentation because of significant mass effects with obstructive hydrocephalus. In all patients cabergoline 1-1.5 mg/wk was started at diagnosis and gradually increased to 0.5 mg daily, aiming for normoprolactinemia. From May 2017 bromocriptine were given to these patients who continued to have hyperprolactinemia despite cabergoline 3.5-4mg/wk. Bromocriptine was commenced 1.25-5mg/day and gradually increased to 10 mg/day on top of cabergoline with careful monitoring of prolactin levels and side effects. Cabergoline was tapered down to 1.5-2mg/wk if prolactin levels remained stable between 2-3x normal while maintaining dose of bromocriptine. In M1, cabergoline was tapered off while maintaining bromocriptine 10mg/day with stable prolactin levels (~1000 mIU/L). In M2, normoprolactinemia was achieved after adding on bromocriptine and is currently on cabergoline 2mg/week and bromocriptine 10mg/day. In M3, whose prolactin were 4x normal value despite cabergoline 3.5mg/week, decreased 50% with bromocriptine 5 mg/day and remained stable when cabergoline reduced to 1.5mg/week. F1 had transphenoidal section twice due to failure of medical therapy. Her prolactin remained markedly elevated 10000-20000 mIU/L despite cabergoline 3.5 mg/week and bromocriptine 10mg/day, with persistent bitemporal hemianopia. F2 developed erythema nodosum after starting bromocriptine which was stopped and continued with cabergoline 1 mg/week. F3 showed partial response with 50% reduction in prolactin to 4485 mIU/L with bromocriptine 10 mg/day and cabergoline 1.5mg/week. In patients who underwent debulking, residual tumour remained unchanged. Two patients - tumour shrank 40% (F2) and 90% (M3) with medical therapy alone. In conclusion, adding on bromocriptine can be considered when high dose cabergoline is required for treatment of giant prolactinoma with careful monitoring. This reduces cabergoline dose which saves cost.

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<![CDATA[SAT-270 Priapism Secondary to Cabergoline]]> https://www.researchpad.co/article/elastic_article_6011 Background: Cabergoline and Bromocriptine are ergot derivative long-acting dopamine agonist that are very effective and well tolerated in patients with hyperprolactinemia. A rare and unwanted side effect of Bromocriptine is priapism, which has hardly ever been report in literature and it’s not cited under the medication insert. The underlying mechanism is not totally clear, but it is well known that dopaminergic pathways in the central nervous system are of importance for male sexual behavior and penile erection. Lesser is known about Cabergoline and priapism with only one case report in the literature (1).

Clinical Case: A 65 yr old African American male with a past medical history significant for obesity, essential hypertension, and recent history of frontal headaches was found to have a pituitary macroadenoma. Brain MRI demonstrated 11 x 12 x 9 mm enhancing lesion within the right lateral sella turcica. The lesion extended laterally to abut the right cavernous ICA without vascular encasement or extension into the right temporal skull base. Prolactin level was 276.3 ng/mL (2.1-15.0 ng/mL). He was started on Cabergoline 0.5 mg weekly. 60 days after starting Cabergoline he presented to the ED with a painful penile erection lasting >12 hours. He did not take any Phosphodiesterase (PDE) inhibitors and had no other recent change in medications. He denied any history of sickle cell disease. His most recent dose of Carbergoline was the day prior to the ED visit. He was seen by a Urologist in the ED and confirmed to have a low flow Priapism and underwent aspiration of intracorporal bodies. He was discharged home on pseudoephedrine and pain medications. Carbergoline was discontinued. He has had no further episodes of Priapism since discontinuation of Cabergoline.

Conclusion: The time between drug use and occurrence, absence of other offending medications or precipitating factors and no further priapism episodes once treatment was discontinued suggests a priapism as a rarely reported side effect of Cabergoline. (1)

References:

1.E.de la Pena Zarzuelo, V. Hernandez Canas and C. Llorente Abarca, Department of Urology, Hospital Universitario Fundacion Alcorcon, Madrid, Spain

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<![CDATA[SAT-273 Case of Mistaken Identity?]]> https://www.researchpad.co/article/Ndc6bf340-57dc-4538-9547-70df74d3c4be Introduction Pituitary adenomas occur in 10-15% of patients and the majority are benign. Prolactinomas are the most common form of secretory pituitary adenoma. Pituitary apoplexy, a medical emergency with resulting visual loss and hormonal hyposecretion, requires rapid surgical intervention. We present a case of pituitary macroadenoma that underwent pituitary resection for acute visual disturbance which was later discovered to be caused by undiagnosed demyelinating disease.

Clinical Case Patient is a 32-year-old male who presented initially with complain of fatigue and decreased libido. Work up revealed elevated prolactin level and low testosterone. MRI showed a 2x3cm pituitary macroadenoma. At moment of diagnosis, patient was otherwise asymptomatic. He was started on bromocriptine. During follow up visits, patient reported visual disturbance. First MRI in our clinic showed no suprasellar extension, no impingement of optic chiasm and nonspecific white matter disease. At that time, visual field testing showed left temporal defect in superior quadrant. Follow up MRI 1 year later continued to show a stable macroadenoma without impingement of the optic chiasm, but patient reported progressive left vision disturbance and new right vision loss. He was evaluated in the emergency room where he was treated for pituitary apoplexy with steroids and surgery. Vision improved the next day. Despite uncomplicated post-operative course, patient developed proximal muscle weakness and exam notable for diffuse motor deficit in bilateral lower extremities with hyperreflexia. Endocrinology workup was negative for hypercortisolism and ophthalmology diagnosed him with optic neuropathy. Neurology evaluation led to a diagnosis of multiple sclerosis (MS). Patient was started on natalizumab with complete resolution of all visual and muscle symptoms.

Clinical lesson Our patient presented with complaints of fatigue, decreased libido and work up that showed a macroprolactinoma without MRI evidence of optic chiasm impingement. During treatment, he developed acute visual deficits that were attributed to pituitary apoplexy. This visual disturbance improved after surgery and use of high dose IV steroids, with the latter likely treating what had been an MS flare. In hindsight, ophthalmologic evaluation before surgery had shown new color blindness, a sign of optic neuropathy. Despite temporary relief, patient progressed to develop new muscle weakness and recurrent visual disturbance which led to the diagnosis of MS. Since being diagnosed and treated for MS, he has had complete resolution of his symptoms. This case stresses the importance of considering other etiologies for visual defects in patients with pituitary adenomas.

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<![CDATA[SAT-253 Long-Term Management and Successful Pregnancy of a Patient with a TSH Secreting Macroadenoma Treated with Octreotide]]> https://www.researchpad.co/article/Nb926a8fc-b349-4cd4-998f-022379c7a25c Introduction: TSH-secreting pituitary adenomas (TSHomas) are the rarest form of pituitary tumors. Transsphenoidal surgery is usually the treatment of choice, although somatostatin analogs (SSAs) are a reasonable and effective option. Pregnancy in the setting of TSHomas is an even rarer situation, scarcely reported in the literature. We report the long-term management of a TSHoma treated with octreotide who developed a successful pregnancy.

Case Report: A 16 year-old girl was diagnosed in 2003 with a TSHoma after presenting with goiter, weight loss, tremors and headache. Laboratory tests showed central hyperthyroidism: TSH 2,78 uUI/ml (0,27-4,02); T4 22,4 ng/dl (4,8-12,7); T3 430 ng/dl (72-170) and pituitary MRI showed a 2 cm adenoma. TRH test showed a blunted response, and TSH did not suppress after T3 test, with hormonal values returning to normal range after octreotide administration. Since 2003 the patient have been treated with Octreotide LAR 20 mg. At 34 years-old she expressed her willingness to become pregnant. At this time, hyperthyroidism was controlled (TSH 1.79; T4 12; T3 181) and the pituitary adenoma was smaller (1.2 cm) while on octreotide LAR 20 mg every 8 weeks. Before conceiving, she did a visual field test that was normal and measured α-subunit (αSU), which was slightly increased (0.73 ug/l, upper limit of normal [ULN] < 0.6 ug/l). After 3 months, she successfully conceived. During first trimester, thyroid function remained controlled. The patient was asymptomatic and the fetus was developing as expected. From 18 weeks on, T3 started to increase (T3 227 ng/dl– ULN 200 ng/dl) with normal T4 and FT4 and without symptoms or fetal repercussion. Alpha-subunit increased to 9.5 ug/l. Throughout pregnancy, octreotide was administered in the same pre-pregnancy dosage. At 37 weeks, αSU was 272.314 ug/l after 1:100 dilution (ULN < 604 ug/;) and HCG was 38.316. The patient developed gestational diabetes mellitus that was managed with diet counseling. Spontaneous delivery occurred at 39 weeks, birth weight was 3160g, APGAR 9/10. Newborn thyroid function was normal. Three months after delivery, the patient complained of hand tremors and hair loss. New laboratory tests revealed TSH 6,7 uUI/ml (ULN <4.5); T4 12,9 (ULN <12); T4L 3,3 (ULN <1.7); T3 247 (ULN <200) and αSU was 513 ug/l (ULN< 0.6). Octreotide LAR 20 mg interval was decreased to every 6 weeks. Currently, ten months after delivery, the patients is asymptomatic and thyroid function is normal.

Conclusion: TSHoma appears to be safely managed throughout pregnancy without the need of stopping octreotide, which seems not to adversely affect outcomes for the mother and the fetus. This case also illustrates the long-term management (16 years) of TSHoma with octreotide with excellent hormonal and structural response.

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<![CDATA[SAT-266 Accelerated Osteoporosis - a Rare Presentation of Cushing’s Disease]]> https://www.researchpad.co/article/N91c67f81-744e-4e9e-bd5d-2e6f2f10ff53 <![CDATA[SAT-263 A Vicious Cycle of Hypercortisolism - Cyclical Cushing’s Syndrome]]> https://www.researchpad.co/article/N2615b467-f648-47f7-8522-6460a3167bef 62,500 pg/mL with CRH stimulation. All 3 patients underwent endoscopic transsphenoidal resection by an expert pituitary surgeon with no post-operative complications in patients A & B, but development of partial diabetes insipidus in patient C. In patients A & C, pathology revealed corticotroph hyperplasia while patient B was found to have a corticotroph adenoma. Patients A & B persisted to have symptoms of hypercortisolism, opted to undergo bilateral adrenalectomy and pathology showed diffuse adrenocortical hyperplasia for both. Conclusion: Cyclical CS is likely underdiagnosed because of difficulty in obtaining biochemical confirmation even with strong clinical suspicion of CS. DHEA-S has a long half-life as well as minimal diurnal variation, and could be an additional clue in patients with suspected pituitary source of cyclical hypercortisolism. Ultimately, clinical concern should drive further diagnostic imaging and management. ]]> <![CDATA[SAT-255 Pituitary Adenoma With TSH and GH Co Secretion]]> https://www.researchpad.co/article/N296b9f21-fa76-418d-a630-8ae34812e436 AbstractIntroduction:Thyrotropinomas are rare pituitary adenomas, representing 2% of pituitary tumors.They are characterized by autonomous secretion of thyrotropin (TSH) and elevated levels of peripheral hormones.A third can secrete other hormones, including growth hormone (GH).We present the case of a patient with hypersecretion TSH and GH with clinical manifestations.Clinical case:44-year-old woman with a history of palpitations and weight loss of 8 kilos of 3 months of evolution, as well as decreased visual acuity and headache.Physical exam: tachycardia, fine tremor, prognathism, thickening of the lips, increase in the base of the nose, hands and feet.TSH; 8.8mU / L (0.4-4), FT4: 35.59pg / ml (8-17), GH: 3.93 (less than 1.88), IGF-1: 716ng / ml (101-267), ANTI TPO negative, FSH, LH, Estradiol, Prolactin, Cortisol in range. Thyroid profile is repeated: TSH: 12.92mIU / ml (0.34-4.94); FT4 and T3 high.Campimetry: left temporal hemianopiaPituitary MRI: a heterogeneous 51x42x47mm Turkish chair mass with sphenoid sinus invasion and right cavernosum with vascular structures encompassing.Thyroid ultrasound: normalMethimazole and octeotride LAR are initiated and in June 2018, a transcranial approach and partial resection of the pituitary macroadenoma is performed.In August 2019, hormonal profile IGF1: 470 ng / ml, TSH: 2.7 uUI / ml, T3 207 ng / dl.Pituitary MRI showing evidence of selar, sphenoid expansive lesion with bilateral carotid invasion, bitemporal hemiapnosia, acromegalics facial features and acral growth without signs of hyperthyroidism.Neurosurgery decides to perform a tranesphenoidal approach and partial tumor resection without postoperative complications; The immunohistochemical study reveals GH positive, nonspecific TSH, KI 7% P53 20%. LAR octeotride is suspended.In September 2019, the homonal profile reports IGF1 177ng / ml, TSH: 4.39 uUI / ml, FT4 7.14 ug / dl and T3 50ng / dl, the signs of acromegaly disappear.Discussion.Thyrotropinomas are rare, even more so if they are multi-hormonal, usually they secrete one hormone or another or they are silent. Thyrotropic and somatotropic cells share common transcription factors: Pit-1 and Prop-1.Most of these tumors are silent or manifest clinically with TSH secretion. The case presented has the particularity of expressing clinical characteristics of both GH and TSH secretion.Preoperative treatment with somatostatin analogues can reduce tumor size and control hormonal hypersecretion. Radiation therapy is an alternative in case of unsatisfactory results after surgery.Multi-hormonality predicts a higher risk of recurrence than the secretory tumors of only one hormone, so monitoring these patients is essential. ]]>