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Open access

Athanasios Gkirgkinoudis, Christina Tatsi, Stephanie J DeWard, Bethany Friedman, Fabio R Faucz, and Constantine A Stratakis

Summary

SOX5 plays an important role in chondrogenesis and chondrocyte differentiation. SOX5 defects in humans (often deletions) result in a Lamb-Shaffer syndrome (LSS), presenting with speech delay, behavioral problems and minor dysmorphic features. We present a patient with idiopathic short stature (ISS) who carried a heterozygous novel variant in SOX5. The patient had no dysmorphic features, but a skeletal survey revealed minor skeletal abnormalities. Laboratory and endocrine evaluation for known causes of growth disorders was negative. The missense variant in SOX5 gene (c.1783A>G, p.K595E) was de novo and was predicted to be deleterious by in silico programs. In summary, we present a patient whose presentation may provide evidence that gene defects in SOX5 may contribute to the etiology of short stature and/or mild skeletal defects beyond LSS.

Learning points:

  • We report a girl with idiopathic short stature and mild skeletal defects presenting with a de novo variant in SOX5 gene, predicted in silico to be deleterious.

  • Although SOX5 has not been previously specifically associated with short stature, several evidences support its contributing effect on dyschondrogenesis.

  • Missense variants in SOX5 gene may lead to mild phenotypes, differing from typical presentation of patients with Lamb-Shaffer syndrome.

Open access

Omayma Elshafie and Nicholas Woodhouse

Summary

A 79-year-old male presented with a 10-year history of intermittent headache, sweating, persistent hand numbness and uncontrolled hypertension. He was receiving Nifedipine and Hydrochorothizide. On examination (O/E), his BP was 180/100 he was acromegalic. His growth hormone (GH) was 10 mIU/L (0.0–0.1) and his insulin-like growth factor (IGF-1): 952 µg/L (76–160). An MRI of the pituitary revealed a 3 × 2 cm pituitary macroadenoma. Surgery was refused and the family agreed for a therapeutic trial of octreotide. His GH levels fell immediately. Two weeks later he was switched to long-acting monthly octreotide in September 2003. During his 16-year follow-up, he has remained well and asymptomatic off medications for hypertension. His BP and IGF-1 levels were also normal until octreotide Long acting (LA) octrotide was stopped for 3 months at age 96. During this period the IGF-1 level returned to pretreatment levels 500 ng/L (50–141), GH 24 mIU/L (0.0–0.1), and a small residual tumour 0.5–0.8 cm was seen on the MRI. Octreotide LA was restarted and the IGF-1 and GH levels returned to normal. He continues the same treatment to date age 97 without side effects. We conclude that the successful control of IGF-1, GH levels, hypertension, tumour size and clinical symptoms for more than 16 years occurred using octreotide LA in an elderly advanced acromegalic patient. To the best of our knowledge, this is the first report of the successful use of octreotide LA for more than 16 years.

Learning points:

  • The value of a therapeutic trial of octreotide to identify responders.

  • Control of GH and IGF-1 secretion using octreotide LA.

  • The report of the successful use of octreotide for more than 16 years irrespective of age.

Open access

Milad Darrat, Mohammad Binhussein, Alan Beausang, Clare Faul, Michael W O’Reilly, Mohsen Javadpour, and Amar Agha

Pituitary adenomas are the commonest sellar tumours. Pituitary metastases are very rare, with the most common primaries being breast and lung cancers. We report the case of an 83-year-old man with a history of breast carcinoma who presented with recent-onset headaches and progressive deterioration of visual acuity. MRI brain showed a large sellar and suprasellar mass compressing the optic chiasm and involving the pituitary stalk. Transsphenoidal debulking resulted in symptomatic relief and visual recovery. Specimen examination revealed a combination of a gonadotroph pituitary adenoma that was infiltrated by metastatic breast carcinoma. He had no symptoms of diabetes insipidus. He was subsequently treated with pituitary radiotherapy. This is a very rare presentation of a pituitary mass with mixed pathology. To our knowledge, this is the third description of a breast carcinoma metastasis into a gonadotroph cell pituitary adenoma.

Learning points:

  • Infiltrating metastases into pituitary adenomas are very rare but do occur.

  • To our knowledge this is the third case of breast adenocarcinoma metastasising to a gonadotroph pituitary adenoma.

  • Pituitary metastases should always be considered in rapidly evolving pituitary symptoms in a cancer patient.

  • Not all complex pituitary lesions are associated with panhypopituitarism.

  • Early invasive local management (TSS and post TSS radiotherapy) can provide rapid satisfactory outcomes.

Open access

Farooq Khan and Mary Jane Brassill

Summary

There is emerging evidence of an association between COVID-19 vaccination and subacute thyroiditis. We present the case of a 42-year-old female healthcare worker who was diagnosed with subacute thyroiditis 4 days after receiving her second dose of Pfizer-BioNTech vaccine. Her clinical course followed the classical pattern for thyroiditis with spontaneous return to euthyroidism at 6 months post-presentation. The autoimmune/inflammatory syndrome induced by adjuvants has been implicated as a cause of autoimmune conditions post-vaccination and is a potential mechanism for subacute thyroiditis in our case.

Learning points

  • Subacute thyroiditis should be considered in all patients who receive any kind of vaccine for COVID-19 and subsequently develop symptoms or signs of hyperthyroidism or neck pain.

  • Subacute thyroiditis is a self-limiting condition, and recognising it is important as no specific thyroid treatment (antithyroid drugs or thyroid hormone replacement) is necessary for most patients.

  • The autoimmune/inflammatory syndrome induced by adjuvants may be an under-recognised cause of endocrinopathies and should particularly be considered post-vaccination.

Open access

Vincent Amodru, Thierry Brue, and Frederic Castinetti

Summary

Here, we describe a case of a patient presenting with adrenocorticotrophic hormone-independent Cushing’s syndrome in a context of primary bilateral macronodular adrenocortical hyperplasia. While initial levels of cortisol were not very high, we could not manage to control hypercortisolism with ketoconazole monotherapy, and could not increase the dose due to side effects. The same result was observed with another steroidogenesis inhibitor, osilodrostat. The patient was finally successfully treated with a well-tolerated synergitic combination of ketoconazole and osilodrostat. We believe this case provides timely and original insights to physicians, who should be aware that this strategy could be considered for any patients with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.

Learning points

  • Ketoconazole–osilodrostat combination therapy appears to be a safe, efficient and well-tolerated strategy to supress cortisol levels in Cushing syndrome.

  • Ketoconazole and osilodrostat appear to act in a synergistic manner.

  • This strategy could be considered for any patient with uncontrolled hypercortisolism and delayed or unsuccessful surgery, especially in the context of the COVID-19 pandemic.

  • Considering the current cost of newly-released drugs, such a strategy could lower the financial costs for patients and/or society.

Open access

Clare Miller, Agnieszka Pazderska, John Reynolds, Patricia Gou, Barbara Dunne, Kealan McElhinney, and Lisa Owens

Summary

A 53-year-old female presented to a tertiary ophthalmology referral centre complaining of unilateral painless loss of vision. Subsequent assessment revealed malignant hypertension causing right-sided cystoid macular oedema. During the course of secondary hypertension workup, she was diagnosed with a 7.8 cm phaeochromocytoma which was resected. Testing for a panel of all predisposing phaeochromocytoma-causing variants using next-generation sequencing resulted in the diagnosis of a novel SDHD variant.

Learning points

  • Screening for secondary causes of hypertension is indicated when there is evidence of hypertension-mediated end-organ damage ().

  • Testing for a predisposing variant should be considered in all patients with phaeochromocytoma or paraganglioma due to the high heritability rate and prevalence of somatic variants (, , ).

  • Novel variants are commonly uncovered in the Succinate Dehydrogenase (SDH) subunit; proving pathogenicity is a complex, time-consuming process and one challenge of next-generation sequencing ().

  • SDHB immunohistochemistry as a tool for demonstrating pathogenicity is associated with reduced sensitivity when assessing SDHD variants (, ).

Open access

Diana Festas Silva, Adriana De Sousa Lages, Joana Serra Caetano, Rita Cardoso, Isabel Dinis, Leonor Gomes, Isabel Paiva, and Alice Mirante

Summary

Hypoparathyroidism is characterized by low or inappropriately normal parathormone production, hypocalcemia and hyperphosphatemia. Autosomal dominant hypocalcemia (ADH) type 1 is one of the genetic etiologies of hypoparathyroidism caused by heterozygous activating mutations in the calcium-sensing receptor (CASR) gene. Current treatments for ADH type 1 include supplementation with calcium and active vitamin D. We report a case of hypoparathyroidism in an adolescent affected by syncope without prodrome. The genetic testing revealed a variant in the CASR gene. Due to standard therapy ineffectiveness, the patient was treated with recombinant human parathyroid hormone (1–34), magnesium aspartate and calcitriol. He remained asymptomatic and without neurological sequelae until adulthood. Early diagnosis and treatment are important to achieve clinical stability.

Learning points

  • Autosomal dominant hypocalcemia (ADH) type 1 is one of the genetic etiologies of hypoparathyroidism caused by heterozygous activating mutations in the calcium-sensing receptor (CASR) gene.

  • The variant c.368T>C (p.Leu123Ser) in heterozygosity in the CASR gene is likely pathogenic and suggests the diagnosis of ADH type 1.

  • Teriparatide (recombinant human parathyroid hormone 1–34) may be a valid treatment option to achieve clinical stability for those individuals whose condition is poorly controlled by current standard therapy.

Open access

Jennifer R Snaith, Duncan McLeod, Arthur Richardson, and David Chipps

Summary

Insulinomatosis is a rare cause of hyperinsulinaemic hypoglycaemia. The ideal management approach is not known. A 40-year-old woman with recurrent symptomatic hyperinsulinaemic hypoglycaemia was diagnosed with an insulinoma. A benign 12 mm pancreatic head insulinoma was resected but hypoglycaemia recurred 7 years later. A benign 10 mm pancreatic head insulinoma was then resected but hypoglycaemia recurred within 2 months. Octreotide injections were trialled but exacerbated hypoglycaemia. After a 2-year interval, she underwent total pancreatectomy. A benign 28 mm pancreatic head insulinoma was found alongside insulin-expressing monohormonal endocrine cell clusters (IMECCs) and islet cell hyperplasia, consistent with a diagnosis of insulinomatosis. Hypoglycaemia recurred within 6 weeks. There was no identifiable lesion on MRI pancreas, Ga-68 PET or FDG PET. Diazoxide and everolimus were not tolerated. MEN-1 testing was negative. Insulinomatosis should be suspected in insulinomas with early recurrence or multifocality. De novo lesions can arise throughout the pancreas. Extensive surgery will assist diagnosis but may not provide cure.

Learning points:

  • Insulinomas are usually benign and managed surgically.

  • Insulinomatosis is characterised by multifocal benign insulinomas with a tendency to recur early. It is rare.

  • Multifocal or recurrent insulinomas should raise suspicion of MEN-1 syndrome, or insulinomatosis.

  • Insulinomatosis is distinguished histologically by insulin-expressing monohormonal endocrine cell clusters (IMECCs) and tumour staining only for insulin, whereas MEN-1 associated insulinomas stain for multiple hormones.

  • The ideal treatment strategy is unknown. Total pancreatectomy may not offer cure.

Open access

Giuseppina Molinaro, Renato De Vecchis, Elio Badolati, and Raffaele Giannattasio

Summary

The authors examine several reports of the literature concerning thyrotoxic dilated cardiomyopathy. In particular, it is pointed out that this clinical manifestation of hyperthyroidism is rare in readily diagnosed and properly treated hyperthyroidism. Case reports are analyzed comparatively. A case deriving from the direct experience of the authors is also presented.

Learning points:

  • Dilated cardiomyopathy has been reported as the initial presentation of hyperthyroidism in only 6% of patients although <1% developed severe LV dysfunction.

  • Clinical picture of thyrotoxic dilated cardiomyopathy can degenerate into an overt cardiogenic shock sometimes requiring the use of devices for mechanical assistance to the circulation, or extracorporeal membrane oxygenation.

  • For thyrotoxic dilated cardiomyopathy, evidence-based pharmacologic measures valid for heart failure should always be supplemented by the administration of specific thyroid therapies such as thionamides (methimazole, carbimazole or propylthiouracil), whose relatively long latency of action should be supported by the i.v. administration of small doses of beta-blocker.

  • In cases of cardiogenic shock, the administration of beta-blocker should be carried out only after the restoration of satisfactory blood pressure levels- with the prudent use of synthetic catecholamines, if necessary.

Open access

Stine Bech Smedegaard and Mads Vandsted Svart

Summary

Excessive intake of licorice may cause pseudohyperaldosteronism which, in turn, may lead to hypertension and hypokalemia. Severe hypokalemia may lead to electrocardiogram (ECG) changes including long QT interval potentially progressing into malignant arrhythmias. Here we present a 43-year-old woman admitted to the hospital with chest pain and a stinging sensation in the upper extremities. Her peak blood pressure was 177/98 mmHg and the blood test revealed low plasma potassium of 1.9 mmol/L. The ECG revealed flattened T-waves and long QT interval. Prior to admission, the patient had increased licorice ingestion to a total of some 70 g daily. The licorice intake was stopped and potassium was administrated orally and intravenously. Plasma potassium normalized and the ECG changes remitted. To our knowledge a few other cases of licorice-induced pseudohyperaldosteronism and long QT interval have previously been reported. This underlines the importance of quantifying licorice intake in younger people with unexplained high blood pressure and low potassium.

Learning points:

  • Even small amounts of licorice daily may increase the risk of developing hypertension; therefore, licorice should be asked for specifically.

  • Even though licorice intake is very easy to cover in the patient’s history, it is often missed.

  • Excessive licorice intake may course severe hypokalemia causing long QT interval in the ECG recording, potentially progressing into arrhythmias and even cardiac arrest/sudden death.

  • Hypokalemia <3 mmol/L and present ECG changes should be treated with potassium intravenously.

  • Licorice-induced hypertension may be associated with syndrome of apparent mineralocorticoid excess (SAME). Plasma renin and aldosterone are both low at diagnosis and normalize when licorice is stopped.