Growth Hormone (GH) and Thyroid Stimulating Hormone (TSH) Co-Secreting Pituitary Macroadenoma

Background: TSH secreting pituitary adenomas are rare and accounts for 0.5-3% of all pituitary adenomas. Only 20-25% of those adenomas co-secrete other hormones like growth hormone or prolactin. Mixed GH and TSH secreting adenomas present with symptoms from tumor growth and features of both acromegaly and hyperthyroidism. Clinical Case: A 57 years old woman with a past medical history of chronic joint pains and bilateral knee swelling presented to her PCP with complaints of chronic fatigue. Evaluation revealed a normal TSH level and MNG and patient did not have any further work-up. She reported undergoing periodic knee arthrocentesis which gave her only temporary pain relief. Two years later, patient presented with complaints of unintentional weight loss, tremors and palpitations. She also reported enlargement in the size of hands, feet and forehead and no improvement in the knee swelling after multiple arthrocentesis. Lab evaluation revealed high free T4 2.31ng/dl (0.58-1.64), high free T3 6.44pg/ml (2.50-4.30), non-suppressed TSH 1.32mU/L (0.34-5.00), elevated IGF-1 415ng/ml (47-236), GH 7.76ng/ml (0.01-3.61) and prolactin 6.69ng/mL (2.74-26.72). Neck USG showed multiple nodules and 24hr radioactive iodine uptake scan showed increased uptake at 43%. 75gm OGTT showed non-suppression of GH level. MRI of brain showed 1.8 cm pituitary macroadenoma. Patient underwent transsphenoidal pituitary resection in January 2018 and the final pathology showed positive tumor staining for GH and TSH. Following surgery, patient reported improvement in symptoms. Lab work-up from October 2018 showed normal IGF 189 ng/ml (47-236), normal GH 0.35(0.01-3.61), Free T4 0.80(0.58-1.64), Free T3 2.41(2.50-4.30), TSH 0.06(0.34-5.00) and MRI from August 2020 showed no evidence of residual pituitary tumor. Conclusion: This is a rare case of a GH and TSH co-secreting pituitary macroadenoma. This case highlights the importance of considering acromegaly early in the differential diagnosis of patients presenting with chronic musculoskeletal symptoms and to pursue work up for central hyperthyroidism in a hyperthyroid patient presenting with a non-suppressed TSH level.

A Case Report on Methimazole-Induced Cholestatic Jaundice in an Elderly Man With Hyperthyroidism

Background: The early detection and diagnosis of the causes of jaundice in a hyperthyroid patient taking antithyroid medications are paramount for the appropriate management of these patients. Clinical Case: A 72 year old male is admitted due to septic shock secondary to pneumonia and funguria, acute kidney injury secondary to sepsis, type 2 diabetes mellitus, uncontrolled and Graves’ disease with thyroid nodules (Tirads 4). On physical examination, he has icteresia and generalized jaundice. Methimazole was started 12 days ago. Initial tests were consistent with a cholestatic pattern of jaundice: slightly elevated alanine aminotransferase 70 U/L (16-63), aspartate aminotransferase 84 U/L (15-37) and significantly elevated alkaline phosphatase 662 U/L (46-116), total bilirubin 12.16 mg/dl (0.20-1.0), conjugated bilirubin 11.29 mg/dl (0-0.20) and unconjugated bilirubin 0.87 mg/dl (0-0.80). He has hypoalbuminemia and normal prothrombin time. He has negative anti-Smith antibody, anti-ribonucleoprotein, anti-mitochondrial antibody, and positive anti-nuclear antibody 1:160 speckled pattern. Hepatitis Profile showed chronic hepatitis A infection. Upper Abdomen Ultrasound showed ill-defined border in the left hepatic lobe; intrahepatic ducts and common bile duct are not dilated; gallbladder is contracted with no evident intraluminal echoes. Whole Abdomen with 4-phase Dynamic Liver CT Scan showed multiple ill-defined hypoattenuating lesions in the entire liver parenchyma; intrahepatic ducts, common bile duct, and pancreatic duct are not dilated; and gallbladder is normal in size without intraluminal calculus with possible metastases at spleen, left adrenal gland and tail of pancreas. He has normal AFP and elevated CEA. Methimazole was discontinued at admission and was started on Hydrocortisone 100 mg/IV every 8 hrs. Repeat liver profile panel showed decreasing trends after 4 days of holding methimazole. Repeat fT4 after 6 days of high dose hydrocortisone showed a decrease from 3.09 ng/dl to 1.98 ng/dl (0.89-1.76). Hydrocortisone was continued and tapered accordingly. Plans for RAI discussed. Conclusion: This case emphasizes the need to be vigilant for the very rare but serious adverse events of antithyroid medications.

Rapid control of thyrotoxicosis for urgent thyroidectomy

<p>Surgery for Grave’s disease is one possible option for definitive treatment. Thyroidectomy is performed after achieving a euthyroid state. Pre-operative preparation of the hyperthyroid patient is essential to avoid peri- and post-operative serious complications due to thyrotoxicosis mainly thyrotoxic crisis and death. The mainstay of preparation is the administration of anti-thyroid drugs. Occasionally rapid pre-operative optimization is required for special reasons (intolerance or side effects to anti-thyroid drugs or an aggravated serious disease with thyrotoxicosis). Various regimens for this aim were suggested with protocols composing various combination iodine (as a Lugol’s solution, or iopanoic acid, or ipodat sodium), steroids, usually dexamethasone and beta blockers, alternatively other options are plasmapheresis, lithium and exchange ionic resin. The restoration of hyperthyroid Grave’s disease to euthyroidism in our patient was rapidly accomplished with iodine, dexamethasone and beta blockers (at seventh day without complications). We propose a possible treatment protocol for these cases.</p>

SAT-576 Possible Involvement of Thyroid Function in PCSK9 Inhibitor Therapy

INTRODUCTION Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition is an effective strategy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol lowering ability of statins. PCSK9, a serine protease that binds to the LDL receptor promoting its degradation, is an important regulator of LDL metabolism. In addition, LDL-cholesterol is also controlled by TSH and thyroid hormones via PCSK9. TSH has received increasing attention as being closely associated with increased LDL-cholesterol level and higher atherosclerotic risks. In vitro study, the effects of TSH on hepatic PCSK9 expression in HepG2 cells were reported (1). I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. This case highlights the involvement of thyroid function in PCSK9 Inhibitor therapy. CLINICAL CASE A 65-year-old man had a weight loss of 6 kg (13 lbs.) in 4 months, accompanied with fatigue. He had a past history of myocardial infarction and his LDL was 83 mg/dL by 2.5mg of rosuvastatin and heart rate was controlled by 10mg of carvedilol. Six months ago, he started a PCSK9 Inhibitor therapy with 140mg of evolocumab every 2 weeks for 6 weeks. He had no preceding viral illness and denied anterior neck pain or tenderness. His height was 1.53 m, weight 52.6 kg (115 lbs.), and body mass index (BMI) 22.46 kg/m2. His thyroid was not enlarged and non-tender without clear palpable thyroid nodules or neck lymph nodes. Hyperthyroidism was suspected and confirmed by thyroid function tests: TSH was less than 0.0005 μIU/mL (normal 0.35–4.94), and free T4 1.830 ng/dL (0.70–1.48). Graves’ disease was considered, and thyroid antibody tests performed. Thyroid peroxidase (TPO) antibody titer was less than 9 IU/mL (&lt;9), and TSI 141% (&lt;120%). To confirm the diagnosis of this hyperthyroid patient, Technetium-99m uptake and scan was done which showed uptake of 0.8% (0.5–7%). After careful observation for 2 months with 5mg of carvedilol, he turned asymptomatic and free T4 lowered to 1.480 ng/dL and TSH remained less than 0.0005 μIU/mL. CLINICAL LESSONS I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. There has been no report of hyperthyroidism induced by PCSK9 inhibitors. Immunological influence of anti-PCSK9 therapy on thyroid is unknown. In this case, the decrease of TSH due to hyperthyroidism was considered to reduce hepatic PCSK9 expression, leading to additive effect to PCSK9 inhibitor. PCSK9 inhibitors may modify the effects of hyperlipidemia treatment by causing changes in thyroid function. When using PCSK9 inhibitors, follow-up of thyroid function should be considered. This case highlights the involvement of thyroid function in PCSK9 inhibitor therapy. Reference (1) Gong, Y., Ma, Y., et al. Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression. Metabolism. 2017;76;32–41

SUN-493 A “Curve Ball” in the Management of an Infertile Hyperthyroid Patient

Introduction: We present the case of a young female patient referred for hyperthyroidism with persistently detectable TSH despite elevated free thyroxine (FT4) levels which, interestingly, failed to normalize following anti-thyroidal treatment. Further testing elucidated the underlying causation for detectable TSH in presence of hyperthyroxinemia to be due to interfering substances in the thyroid function assays. Case: A 35-year-old female is evaluated for hyperthyroidism discovered in preparation for embryo transfer. History includes transient hyperthyroidism two years ago while undergoing in vitro fertilization. Prior workup included negative antibodies and nuclear uptake scan revealing a right-sided autonomously functioning thyroid nodule with 24-hour uptake of 40.7%. She was briefly treated with PTU in first trimester and lost to follow-up. While once again undergoing fertility treatment with clomiphene, the patient developed tremor and heat intolerance. She was found to have TSH 0.3 (0.45-4.12 mU/L) and analog FT4 of 6.4 (0.8-1.8 ng/dL). She denied use of OTC supplements. PTU 50 mg twice daily was initiated with minimal improvement with TSH 0.7 mU/L, FT4 3.7 ng/dL. On evaluation, slight tremor and mild thyroid enlargement were noted. Our differential expanded to include TSH-secreting pituitary adenoma, thyroid hormone resistance (no family history), and assay interference. Both MRI pituitary and an alpha-subunit level (0.36) were normal. Symptoms improved gradually with repeat TSH 1.79 mU/L, FT4 2.4 ng/DL by standard analog methods. We suspected ‘assay interference’ for which FT4 via direct equilibrium dialysis was obtained and was indeed normal at 0.76 ng/dL. Further lab testing verified interference in both in the standard TSH and FT4 assays presumed secondary to heterophile antibodies. Discussion: Interpretation of thyroid studies discordant with the clinical picture or incongruent with each other requires understanding of thyroid physiology and the intricacies of commonly utilized assays. The differential of elevated thyroxine levels with detectable/normal TSH rests between thyroid hormone resistance syndromes, TSH secreting pituitary tumors and interfering substances in the assay. Most commercially available TSH assays are based on a ‘sandwich’ assay which is notoriously interfered with by heterophile antibodies and excess biotin. Determination of FT4 is also challenging as the assay must detect very low concentrations of free hormone relative to excess of protein-bound analyte. When in question, it is important consider utilization of laboratory expertise and retesting by alternative assays.

Graves' Disease and Diabetes Mellitus

Thyroid hormones play an important role in the metabolic propesses. Its disturbances will involve several organs, consequently. A 5 year old girl with Graves' diseases, after several weeks of treatment with propylthiouracil (PTV), developed thyrotoxicosis crisis and diabetes mellitus with ketoacidosis; a condition which is usually fatal. Treatment toward the hyperthyroid state overcome the diabetic stage, eventually. This report is an example of an endocrinological interaction in a hyperthyroid patient. Therefore, the diabetogenic effect of hyperthyroxinemia should not be overlooked.