Summary

Thyroid storm (TS) is a life-threatening condition that may suffer thyrotoxic patients. Therapeutic plasma exchange (TPE) is a rescue approach for TS with acute hepatic failure, but it should be initiated with careful considerations. We present a 55-year-old male patient with untreated Graves’ disease who developed TS. Severe hyperthyroidism and refractory atrial fibrillation with congestive heart failure aggregated to multiple organ failure. The patient was recovered by intensive multimodal therapy, but we had difficulty in introducing TPE treatment considering the risk of exacerbation of congestive heart failure due to plasma volume overload. In addition, serum total bilirubin level was not elevated in the early phase to the level of indication for TPE. The clinical course of this patient instructed delayed elevation of bilirubin until the level of indication for TPE in some patients and also demonstrated the risk of exacerbation of congestive heart failure by TPE.

Learning points:

• Our patient with thyroid storm could be diagnosed and treated promptly using Japan Thyroid Association guidelines for thyroid storm.

• Delayed elevation of serum bilirubin levels could make the decision of introducing therapeutic plasma exchange difficult in cases of thyroid storm with acute hepatic failure.

• The risk of worsening congestive heart failure should be considered carefully when performing therapeutic plasma exchange.

Summary

Severe hyponatremia and osmotic demyelination syndrome (ODS) are opposite ends of a spectrum of emergency disorders related to sodium concentrations. Management of severe hyponatremia is challenging because of the difficulty in balancing the risk of overcorrection leading to ODS as well as under-correction causing cerebral oedema, particularly in a patient with chronic hypocortisolism and hypothyroidism. We report a case of a patient with Noonan syndrome and untreated anterior hypopituitarism who presented with symptomatic hyponatremia and developed transient ODS.

Learning points:

• Patients with severe anterior hypopituitarism with severe hyponatremia are susceptible to the rapid rise of sodium level with a small amount of fluid and hydrocortisone.

• These patients with chronic anterior hypopituitarism are at high risk of developing ODS and therefore, care should be taken to avoid a rise of more than 4–6 mmol/L per day.

• Early recognition and rescue desmopressin and i.v. dextrose 5% fluids to reduce serum sodium concentration may be helpful in treating acute ODS.

Summary

Lymphocytic hypophysitis is a rare neuroendocrine disease characterised by an autoimmune inflammatory disorder of the pituitary gland. We report a 50-year-old woman who presented with headaches and bilateral sixth cranial nerve palsies. MRI of the pituitary revealed extensive fibrosis involving the sellar and extending into both cavernous sinuses causing bilateral occlusion of the internal carotid arteries (ICA). Transphenoidal biopsy confirmed the diagnosis of infiltrative fibrotic lymphocytic hypophysitis. Symptoms resolved with high dose of oral steroids but relapsed on tapering, requiring several treatments of i.v. pulse steroids over 8 months. Rituximab combined with mycophenolate mofetil was required to achieve long-term symptom relief. Serial MRI pituitary imaging showed stabilisation of her disease without reduction in sellar mass or regression of ICA occlusion. The patient’s brain remained perfused solely by her posterior circulation. This case demonstrates an unusual presentation of a rare disease and highlights a successful steroid-sparing regimen in a refractory setting.

Learning points:

• Lymphocytic hypophysitis is a rare inflammatory disorder of the pituitary gland. In exceptional cases, there is infiltration of the cavernous sinus with subsequent occlusion of the internal carotid arteries.

• First-line treatment of lymphocytic hypophysitis is high-dose glucocorticoids. Relapse after tapering or discontinuation is common and its use is limited by long-term adverse effects.

• There is a paucity of data for treatment of refractory lymphocytic hypophysitis. Goals of treatment should include improvement in symptoms, correction of hormonal insufficiencies, reduction in lesion size and prevention of recurrence.

• Steroid-sparing immunosuppressive drugs such as rituximab and mycophenolate mofetil have been successful in case reports. This therapeutic combination represents a viable alternative treatment for refractory disease.

Summary

Isolated, adult-onset central hypothyroidism is very rare, and its diagnosis can be challenging. A 42-year-old patient was referred for evaluation of a 2.8 cm thyroid nodule. She referred symptoms that could be attributed to hypothyroidism and thyroid tests showed low TSH and normal-low levels of free T4. However, evaluation of the remaining pituitary hormones and pituitary MRI were normal, yet a radionuclide scanning revealed that the thyroid nodule was ‘hot’ and the tracer uptake in the remaining thyroid tissue was suppressed. Interpretation of these studies led to a misdiagnosis of subclinical hyperthyroidism and the patient was treated with radioiodine. Soon after treatment, she developed a frank hypothyroidism without appropriate elevation of TSH and the diagnosis of central hypothyroidism was made a posteriori. Long term follow-up revealed a progressive pituitary failure, with subsequent deficiency of ACTH and GH. This case should alert to the possibility of overlooking central hypothyroidism in patients simultaneously bearing primary thyroid diseases able to cause subclinical hyperthyroidism.

Learning points:

• Although rarely, acquired central hypothyroidism can occur in the absence of other pituitary hormone deficiencies.

• In these cases, diagnosis is challenging, as symptoms are unspecific and usually mild, and laboratory findings are variable, including low, normal or even slightly elevated TSH levels, along with low or low-normal concentrations of free T4.

• In cases with low TSH levels, the coexistence of otherwise common disorders able to cause primary thyroid hyperfunction, such as autonomous nodular disease, may lead to a misdiagnosis of subclinical hyperthyroidism.

Summary

Cushing’s disease is a rare disorder characterised by excessive cortisol production as a consequence of a corticotroph pituitary tumour. While the primary treatment is surgical resection, post-operative radiation therapy may be used in cases of ongoing inadequate hormonal control or residual or progressive structural disease. Despite improved outcomes, radiotherapy for pituitary tumours is associated with hypopituitarism, visual deficits and, rarely, secondary malignancies. We describe an unusual case of a 67-year-old female with presumed Cushing’s disease diagnosed at the age of 37, treated with transsphenoidal resection of a pituitary tumour with post-operative external beam radiotherapy (EBRT), ketoconazole for steroidogenesis inhibition, and finally bilateral adrenalectomy for refractory disease. She presented 30 years after her treatment with a witnessed generalised tonic-clonic seizure. Radiological investigations confirmed an extracranial mass infiltrating through the temporal bone and into brain parenchyma. Due to recurrent generalised seizures, the patient was intubated and commenced on dexamethasone and anti-epileptic therapy. Resection of the tumour revealed a high-grade osteoblastic osteosarcoma. Unfortunately, the patient deteriorated in intensive care and suffered a fatal cardiac arrest following a likely aspiration event. We describe the risk factors, prevalence and treatment of radiation-induced osteosarcoma, an exceedingly rare and late complication of pituitary irradiation. To our knowledge, this is the longest reported latency period between pituitary irradiation and the development of an osteosarcoma of the skull.

Learning points:

• Cushing’s disease is treated with transsphenoidal resection as first-line therapy, with radiotherapy used in cases of incomplete resection, disease recurrence or persistent hypercortisolism.

• The most common long-term adverse outcome of pituitary tumour irradiation is hypopituitarism occurring in 30–60% of patients at 10 years, and less commonly, vision loss and oculomotor nerve palsies, radiation-induced brain tumours and sarcomas.

• Currently proposed characteristics of radiation-induced osteosarcomas include: the finding of a different histological type to the primary tumour, has developed within or adjacent to the path of the radiation beam, and a latency period of at least 3 years.

• Treatment of osteosarcoma of the skull include complete surgical excision, followed by systemic chemotherapy and/or radiotherapy.

• Overall prognosis in radiation-induced sarcoma of bone is poor.

• Newer techniques such as stereotactic radiosurgery may reduce the incidence of radiation-induced malignancies.

Summary

A 53-year-old man who used growth hormone (GH), anabolic steroids and testosterone (T) for over 20 years presented with severe constipation and hypercalcaemia. He had benign prostatic hyperplasia and renal stones but no significant family history. Investigations showed – (1) corrected calcium (reference range) 3.66 mmol/L (2.2–2.6), phosphate 1.39 mmol/L (0.80–1.50), and PTH 2 pmol/L (1.6–7.2); (2) urea 21.9 mmol/L (2.5–7.8), creatinine 319 mmol/L (58–110), eGFR 18 mL/min (>90), and urine analysis (protein 4+, glucose 4+, red cells 2+); (3) creatine kinase 7952 U/L (40–320), positive anti Jo-1, and Ro-52 antibodies; (4) vitamin D 46 nmol/L (30–50), vitamin D3 29 pmol/L (55–139), vitamin A 4.65 mmol/L (1.10–2.60), and normal protein electrophoresis; (5) normal CT thorax, abdomen and pelvis and MRI of muscles showed ‘inflammation’, myositis and calcification; (6) biopsy of thigh muscles showed active myositis, chronic myopathic changes and mineral deposition and of the kidneys showed positive CD3 and CD45, focal segmental glomerulosclerosis and hypercalcaemic tubular changes; and (7) echocardiography showed left ventricular hypertrophy (likely medications and myositis contributing), aortic stenosis and an ejection fraction of 44%, and MRI confirmed these with possible right coronary artery disease. Hypercalcaemia was possibly multifactorial – (1) calcium release following myositis, rhabdomyolysis and acute kidney injury; (2) possible primary hyperparathyroidism (a low but detectable PTH); and (3) hypervitaminosis A. He was hydrated and given pamidronate, mycophenolate and prednisolone. Following initial biochemical and clinical improvement, he had multiple subsequent admissions for hypercalcaemia and renal deterioration. He continued taking GH and T despite counselling but died suddenly of a myocardial infarction.

Learning points:

• The differential diagnosis of hypercalcaemia is sometimes a challenge.

• Diagnosis may require multidisciplinary expertise and multiple and invasive investigations.

• There may be several disparate causes for hypercalcaemia, although one usually predominates.

• Maintaining ‘body image’ even with the use of harmful drugs may be an overpowering emotion despite counselling about their dangers.

Summary

In this case report, we describe a 37-year-old male who presented with fever and tender neck mass. Neck ultrasonography revealed a mixed echogenic multiloculated solid-cystic lesion containing turbid fluid and occupying the right thyroid region. Thyroid function tests showed subclinical hyperthyroidism. The patient was initially diagnosed with thyroid abscess and he was subsequently treated with percutaneous aspiration and i.v. antibiotics; however, his clinical symptoms did not improve. Surgical treatment was then performed and a pathological examination revealed a ruptured epidermoid cyst with abscess formation. No thyroid tissue was identified in the specimen. The patient was discharged uneventfully. However, at the 3-month and 1-year follow-ups, the patient was discovered to have developed subclinical hypothyroidism. Neck ultrasonography revealed a normal thyroid gland. This report demonstrates a rare case of epidermoid cyst abscess in the cervical region, of which initial imaging and abnormal thyroid function tests led to the erroneous diagnosis of thyroid abscess.

Learning points:

• Epidermoid cyst abscess at the cervical region can mimic thyroid abscess.

• Neck ultrasonography cannot distinguish thyroid abscess from epidermoid cyst abscess.

• Thyroid function may be altered due to the adjacent soft tissue inflammation.

Summary

Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described as a rare cause of pituitary apoplexy, a potentially life-threatening clinical condition. We report the case of a 69-year-old man with a known pituitary macroadenoma who was diagnosed with prostate cancer and started treatment with GnRH agonist leuprorelin (other hormones were not tested before treatment). Few minutes after drug administration, the patient presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Pituitary MRI revealed tumor enlargement and T1-hyperintense signal, compatible with recent bleeding sellar content. Laboratory endocrine workup was significant for low total testosterone. The patient was managed conservatively with high-dose steroids, and symptoms significantly improved. This case describes a rare phenomenon, pituitary apoplexy induced by GnRH agonist. We review the literature regarding this condition: the pathophysiological mechanism involved is not clearly established and several hypotheses have been proposed. Although uncommon, healthcare professionals and patients should be aware of this complication and recognize the signs, preventing a delay in diagnosis and treatment.

Learning points:

• Pituitary apoplexy (PA) is a potentially life-threatening complication that can be caused by gonadotropin-releasing hormone agonist (GnRHa) administration for the treatment of advanced prostate cancer.

• This complication is rare but should be taken into account when using GnRHa, particularly in the setting of a known pre-existing pituitary adenoma.

• PA presents with classic clinical signs and symptoms that should be promptly recognized.

• Patients should be instructed to seek medical care if suspicious symptoms occur.

• Healthcare professionals should be aware of this complication, enabling its early recognition, adequate treatment and favorable outcome.

Summary

Standard treatment of hypoparathyroidism consists of supplementation of calcium and vitamin D analogues, which does not fully restore calcium homeostasis. In some patients, hypoparathyroidism is refractory to standard treatment with persistent low serum calcium levels and associated clinical complications. Here, we report on three patients (58-year-old male, 52-year-old female, and 48-year-old female) suffering from severe treatment-refractory postsurgical hypoparathyroidism. Two patients had persistent hypocalcemia despite oral treatment with up to 4 µg calcitriol and up to 4 g calcium per day necessitating additional i.v. administration of calcium gluconate 2–3 times per week, whereas the third patient presented with high frequencies of hypocalcemic and treatment-associated hypercalcemic episodes. S.c. administration of rhPTH (1–34) twice daily (40 µg/day) or rhPTH (1–84) (100 µg/day) only temporarily increased serum calcium levels but did not lead to long-term stabilization. In all three cases, treatment with rhPTH (1–34) as continuous s.c. infusion via insulin pump was initiated. Normalization of serum calcium and serum phosphate levels was observed within 1 week at daily 1–34 parathyroid hormone doses of 15 µg to 29.4 µg. Oral vitamin D and calcium treatment could be stopped or reduced and regular i.v. calcium administration was no more necessary. Ongoing efficacy of this treatment has been documented for up to 7 years so far. Therefore, we conclude that hypoparathyroidism that is refractory to both conventional treatment and s.c. parathyroid hormone (single or twice daily) may be successfully treated with continuous parathyroid hormone administration via insulin pump.

Learning points:

• Standard treatment of hypoparathyroidism still consists of administration of calcium and active vitamin D.

• Very few patients with hypoparathyroidism also do not respond sufficiently to standard treatment or administration of s.c. parathyroid hormone once or twice daily.

• In those cases, continuous s.c. administration of parathyroid hormone via insulin pump may represent a successful treatment alternative.

Summary

The etiology of hyponatremia is assessed based on urine osmolality and sodium. We herein describe a 35-year-old Asian man with pulmonary tuberculosis and perforated duodenal ulcer who presented with hyponatremia with hourly fluctuating urine osmolality ranging from 100 to 600 mosmol/kg, which resembled urine osmolality observed in typical polydipsia and SIADH simultaneously. Further review revealed correlation of body temperature and urine osmolality. Since fever is a known non-osmotic stimulus of ADH secretion, we theorized that hyponatremia in this patient was due to transient ADH secretion due to fever. In our case, empiric exogenous glucocorticoid suppressed transient non-osmotic ADH secretion and urine osmolality showed highly variable concentrations. Transient ADH secretion-related hyponatremia may be underrecognized due to occasional empiric glucocorticoid administration in patients with critical illnesses. Repeatedly monitoring of urine chemistries and interpretation of urine chemistries with careful review of non-osmotic stimuli of ADH including fever is crucial in recognition of this etiology.

Learning points:

• Hourly fluctuations in urine osmolality can be observed in patients with fever, which is a non-osmotic stimulant of ADH secretion.

• Repeated monitoring of urine chemistries aids in the diagnosis of the etiology underlying hyponatremia, including fever, in patients with transient ADH secretion.

• Glucocorticoid administration suppresses ADH secretion and improves hyponatremia even in the absence of adrenal insufficiency; the etiology of hyponatremia should be determined carefully in these patients.