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Open access

Anne Marie Hannon, Isolda Frizelle, George Kaar, Steven J Hunter, Mark Sherlock, Christopher J Thompson, Domhnall J O’Halloran and the Irish Pituitary Database Group

Summary

Pregnancy in acromegaly is rare and generally safe, but tumour expansion may occur. Managing tumour expansion during pregnancy is complex, due to the potential complications of surgery and side effects of anti-tumoural medication. A 32-year-old woman was diagnosed with acromegaly at 11-week gestation. She had a large macroadenoma invading the suprasellar cistern. She developed bitemporal hemianopia at 20-week gestation. She declined surgery and was commenced on 100 µg subcutaneous octreotide tds, with normalisation of her visual fields after 2 weeks of therapy. She had a further deterioration in her visual fields at 24-week gestation, which responded to an increase in subcutaneous octreotide to 150 µg tds. Her vision remained stable for the remainder of the pregnancy. She was diagnosed with gestational diabetes at 14/40 and was commenced on basal bolus insulin regimen at 22/40 gestation. She otherwise had no obstetric complications. Foetal growth continued along the 50th centile throughout pregnancy. She underwent an elective caesarean section at 34/40, foetal weight was 3.2 kg at birth with an APGAR score of 9. The neonate was examined by an experienced neonatologist and there were no congenital abnormalities identified. She opted not to breastfeed and she is menstruating regularly post-partum. She was commenced on octreotide LAR 40 mg and referred for surgery. At last follow-up, 2 years post-partum, the infant has been developing normally. In conclusion, our case describes a first presentation of acromegaly in pregnancy and rescue of visual field loss with somatostatin analogue therapy.

Learning points:

  • Tumour expansion may occur in acromegaly during pregnancy.

  • Treatment options for tumour expansion in pregnancy include both medical and surgical options.

  • Somatostatin analogues may be a viable medical alternative to surgery in patients with tumour expansion during pregnancy.

Open access

Philip D Oddie, Benjamin B Albert, Paul L Hofman, Craig Jefferies, Stephen Laughton and Philippa J Carter

Summary

Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP.

Learning points:

  • Adrenocortical carcinoma is an important differential diagnosis for virilization in young children

  • Mitotane is a chemotherapeutic agent that is used to treat adrenocortical carcinoma and causes adrenal necrosis

  • Mitotane is an endocrine disruptor. In addition to the intended effect of adrenal insufficiency, it can cause hypothyroidism, with gynecomastia also reported in adults.

  • Patients taking mitotane require very high doses of hydrocortisone replacement therapy because mitotane interferes with steroid metabolism. This effect persists after mitotane therapy is completed

  • In our case, mitotane caused peripheral precocious puberty, possibly through its estrogenic effect.

Open access

Charlotte S Schömig, Marie-Ève Robinson and Julia E von Oettingen

Summary

Congenital hypothyroidism requires prompt treatment to prevent adverse health outcomes. Poor intestinal levothyroxine absorption can complicate management. We present a case of a term female newborn with necrotizing enterocolitis (NEC) requiring subtotal ileum resection. Congenital hypothyroidism was diagnosed by newborn screening. Treatment was complicated by intestinal malabsorption of levothyroxine. Intravenous levothyroxine substitution restored euthyroidism and supraphysiologic PO doses subsequently maintained a euthyroid state. After several months, the required levothyroxine dose was weaned down to typical recommended dosing. In conclusion, small bowel resection secondary to NEC may lead to malabsorption of oral levothyroxine. An intravenous levothyroxine dose of approximately 50% typical PO dosing is effective in providing rapid normalization of free T4 and TSH. High PO doses may be required to maintain euthyroidism. Close thyroid function monitoring and immediate therapy adjustment are essential as the individual absorption may vary widely. Normal absorption levels may be regained due to adaption of the neonatal intestines.

Learning points:

  • In neonates with malabsorption after ileum resection intravenous levothyroxine replacement should be used to provide normalization of free T4 and TSH.

  • Very high doses of up to 500% usual oral levothyroxine may be required to maintain euthyroidism. The estimated degree of malabsorption can be used to determine the initial dose.

  • Close thyroid function monitoring and immediate therapy adjustment are essential as the absorption and intestinal adaption may vary widely.

Open access

Varalaxmi Bhavani Nannaka and Dmitry Lvovsky

Summary

Angina pectoris in pregnancy is unusual and Prinzmetal’s angina is much rarer. It accounts for 2% of all cases of angina. It is caused by vasospasm, but the mechanism of spasm is unknown but has been linked with hyperthyroidism in some studies. Patients with thyrotoxicosis-induced acute myocardial infarction are unusual and almost all reported cases have been associated with Graves’ disease. Human chorionic gonadotropin hormone-induced hyperthyroidism occurs in about 1.4% of pregnant women, mostly when hCG levels are above 70–80 000 IU/L. Gestational transient thyrotoxicosis is transient and generally resolves spontaneously in the latter half of pregnancy, and specific antithyroid treatment is not required. Treatment with calcium channel blockers or nitrates reduces spasm in most of these patients. Overall, the prognosis for hyperthyroidism-associated coronary vasospasm is good. We describe a very rare case of an acute myocardial infarction in a 27-year-old female, at 9 weeks of gestation due to right coronary artery spasm secondary to gestational hyperthyroidism with free thyroxine of 7.7 ng/dL and TSH <0.07 IU/L.

Learning points:

  • AMI and cardiac arrest due to GTT despite optimal medical therapy is extremely rare.

  • Gestational hyperthyroidism should be considered in pregnant patients presenting with ACS-like symptoms especially in the setting of hyperemesis gravidarum.

  • Our case highlights the need for increased awareness of general medical community that GTT can lead to significant cardiac events. Novel methods of controlling GTT as well as medical interventions like ICD need further study.

Open access

Julian Choi, Perin Suthakar and Farbod Farmand

Summary

We describe the case of a young Hispanic female who presented with thyrotoxicosis with seizures and ischemic stroke. She was diagnosed with a rare vasculopathy – moyamoya syndrome. After starting antithyroid therapy, her neurologic symptoms did not improve. Acute neurosurgical intervention had relieved her symptoms in the immediate post-operative period after re-anastomosis surgery. However, 2 post-operative days later, she was found to be in status epilepticus and in hyperthyroid state. She quickly deteriorated clinically and had expired a few days afterward. This is the second case in literature of a fatality in a patient with moyamoya syndrome and Graves’ disease. However, unlike the other case report, our patient had undergone successful revascularization surgery. We believe her underlying non-euthyroid state had potentiated her clinical deterioration. Case studies have shown positive correlation between uncontrolled hyperthyroidism and stroke-like symptoms in moyamoya syndrome. Mostly all patients with these two disease processes become symptomatic in marked hyperthyroid states. Thus, it may be either fluctuations in baseline thyroid function or thyrotoxicosis that potentiate otherwise asymptomatic moyamoya vasculopathy.

Learning points:

  • Awareness of the association between Graves’ disease and moyamoya syndrome in younger patients presenting with stroke-like symptoms.

  • Obtaining euthyroid states before undergoing revascularization surgery may protect the patient from perioperative mortality and morbidity.

  • Although moyamoya disease is usually thought to be genetically associated, there are reports that thyroid antibodies may play a role in its pathogenesis and have an autoimmune link.

  • Fluctuations in baseline thyroid function for patients with known Graves’ disease may be a potentiating factor in exacerbating moyamoya vasculopathy.

Open access

Chun-Han Lo and Ding-Ping Sun

Summary

Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Traditionally, inappropriately elevated levels of insulin in the face of hypoglycemia are the key to diagnosis. However, contradictory levels of insulin and C-peptide do not necessarily exclude the diagnosis. A 50-year-old female was brought to our emergency department because of conscious disturbance on the previous night. She had no history of diabetes mellitus, and was not using any medications or alcohol. Laboratory data showed low sugar, a significantly low insulin level, and elevated C-peptide. After admission, she had multiple episodes of spontaneous hypoglycemia after overnight fasts without discomfort. It was considered that a neuroendocrine tumor was the source of her hypoglycemia. CT scan of the abdomen revealed a 1.1cm hypervascular nodule in the pancreatic tail. Elective laparoscopic distal pancreatectomy was incorporated into her treatment course. A 1.2×1.0cm homogenous well-encapsulated tumor was resected. We monitored her glucose levels in the outpatient clinic every month for a period of six months. She did not have another episode of spontaneous hypoglycemia.

Learning points

  • Insulinoma causes endogenous hypoglycemia – it cannot be ruled out in patients presenting with hypoglycemia and low insulin levels; history and imaging studies should be done for further assessment

  • A 24-h fast test has the same clinical significance as that of 72-h fast test

  • C-peptide is a useful biochemical marker in addition to serum insulin, which can be used to diagnose insulinomas

  • CT scan is used to measure the tumor size and localize the tumor. However, definitive diagnosis is only achieved through histopathologic evaluation of diseased tissue

Open access

Luísa Correia Martins, Ana Rita Coutinho, Mónica Jerónimo, Joana Serra Caetano, Rita Cardoso, Isabel Dinis and Alice Mirante

Summary

Alternating between hyper- and hypo-thyroidism may be explained by the simultaneous presence of both types of TSH receptor autoantibodies (TRAbs) – thyroid stimulating autoantibodies (TSAbs) and TSH blocking autoantibodies (TBAbs). It is a very rare condition, particulary in the pediatric age. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. Many mechanisms may be involved in fluctuating thyroid function: hormonal supplementation, antithyroid drugs and levels of TSAbs and TBAbs. Frequent dose adjustments are needed in order to achieve euthyroidism. A definitive therapy may be necessary to avoid switches in thyroid function and frequent need of therapeutic changes. We describe an immune-mediated case of oscillating thyroid function in a 13-year-old adolescent. After a short period of levothyroxine treatment, the patient switched to a hyperthyroid state that was only controlled by adding an antithyroid drug.

Learning points

  • Autoimmune alternating hypo- and hyper-thyroidism is a highly uncommon condition in the pediatric age.

  • It may be due to the simultaneous presence of both TSAbs and TBAbs, whose activity may be estimated in vitro through bioassays.

  • The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time.

  • The management of this condition is challenging, and three therapeutic options could be considered: I-131 ablation, thyroidectomy or pharmacological treatment (single or double therapy).

  • Therapeutic decisions should be taken according to clinical manifestations and thyroid function tests, independent of the bioassays results.

  • A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment.

Open access

Christine Yu, Inder J Chopra and Edward Ha

Summary

Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumor activity and significant autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in treatment of immune-related adverse events; however, a concern regarding the property of steroids to reduce therapeutic antitumor response exists. This study describes the first reported case of ipilimumab-associated thyroid storm and implicates iopanoic acid as an alternative therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic melanoma presented with fatigue, anorexia, decreased functional status, and intermittent diarrhea for several months, shortly after initiation of ipilimumab – a recombinant human monoclonal antibody to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival, she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet non-toxic appearing. She had diffuse, non-tender thyromegaly. An electrocardiogram (EKG) revealed supraventricular tachycardia. Blood, urine, and stool cultures were collected, and empiric antibiotics were started. A computed tomography (CT) angiogram of the chest was negative for pulmonary embolism or pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted thyroid function testing. TSH was decreased at 0.16 μIU/ml (normal 0.3–4.7); free tri-iodothyronine (T3) was markedly elevated at 1031 pg/dl (normal 249–405), as was free thyroxine (T4) at 5.6 ng/dl (normal 0.8–1.6). With iopanoic acid and methimazole therapy, she markedly improved within 48 h, which could be attributed to lowering of serum T3 with iopanoic acid rather than to any effect of the methimazole. Ipilimumab is a cause of overt thyrotoxicosis and its immune-mediated adverse effects can be treated with iopanoic acid, a potent inhibitor of T4-to-T3 conversion.

Learning points

  • While ipilimumab more commonly causes autoimmune thyroiditis, it can also cause thyroid storm and clinicians should include thyroid storm in their differential diagnosis for patients who present with systemic inflammatory response syndrome.

  • Immune-related adverse reactions usually occur after 1–3 months of ipilimumab and baseline thyroid function testing should be completed before initiation with ipilimumab.

  • Conflicting data exist on the use of prednisone for treatment of CTLA4 adverse effects and its attenuation of ipilimumab's antitumor effect. Iopanoic acid may be considered as an alternative therapy in this setting.

Open access

Philip C Johnston, Amir H Hamrahian, Richard A Prayson, Laurence Kennedy and Robert J Weil

Summary

A 54-year-old woman presented with bi-temporal hemianopia, palpitations, and diaphoresis. An invasive pituitary macroadenoma was discovered. The patient had biochemical evidence of secondary hyperthyroidism and GH excess; however, she did not appear to be acromegalic. Surgical removal of the pituitary mass revealed a plurihormonal TSH/GH co-secreting pituitary adenoma. TSH-secreting adenomas can co-secrete other hormones including GH, prolactin, and gonadotropins; conversely, co-secretion of TSH from a pituitary adenoma in acromegaly is infrequent.

Learning points

  • This case highlights an unusual patient with a rare TSH/GH co-secreting pituitary adenoma with absence of the clinical features of acromegaly.

  • Plurihormonality does not always translate into the clinical features of hormonal excess.

  • There appears to be a clinical and immunohistochemical spectrum present in plurihormonal tumors.

Open access

Gerald J M Tevaarwerk

Summary

Low triiodothyronine (T3) concentrations in the presence of normal thyroxine (T4) and TSH levels, referred to as the low T3 syndrome (LT3S), are common. LT3S may be caused by starvation, various non-thyroidal illnesses (NTIs) and some medications. Reverse T3 (rT3) concentrations are elevated in the more severely ill, and they characteristically fail to respond to exogenous levothyroxine (l-T4) therapy. The biochemical abnormalities have been explained on the basis of altered peripheral deiodinase activities. Herein, we report on two patients with hypothyroid symptoms who on testing were found to have LT3S. They were atypical clinically in not having LT3S due to any of the usual causes, had no increased rT3 concentrations, and had a normal negative TSH feedback response to l-T4. One (patient 1) had previously been diagnosed with Hashimoto's autoimmune primary hypothyroidism and was on l-T4 therapy. Both had T4 concentrations in the reference range. TSH levels were elevated in patient 1 and in the reference range in patient 2. Starting or increasing l-T4 doses resulted in no clinical improvement and no increase in T3 levels in spite of a marked increase in T4 levels. It is suggested that in the absence of the usual causes, lack of elevated rT3 levels, response to treatment and intact negative TSH feedback these two patients differ from the usual secondary causes of decreases in deiodinase activity. It is speculated that they may represent primary alterations in deiodinase enzymes possibly due to genetic variations in the deiodinase-encoding genes.

Learning points

  • LT3S is commonly found secondary to starvation, NTIs and use of some medications.

  • Low T3 levels are the result of alterations in the activity of deiodinase enzymes.

  • LT3S without the usual causes may represent a primary disturbance in deiodinase activity.