Summary

Comorbidities are a risk factor for patients with COVID-19 and the mechanisms of disease remain unclear. The aim of this paper is to present a case report of an COVID-19 patient with severe hypocalcaemia. This is a report of an 81-year-old female, suffered from myalgia and fatigue for more than 3–4 weeks. Fever and cough appear 2 days before she presented to the emergency room. On physical examination, she was febrile with a temperature of 38.8°C, accompanied by cough, sore throat, headache, fatigue, and muscle ache. Her past medical history was remarkable with no chronic disease. She had lymphopenia. Laboratory test revealed moderate liver dysfunction, hypoalbuminemia, and severe hypocalcaemia (serum corrected calcium level: 5.7  mg/dL). Parathyroid hormone (PTH) was 107.9 pg/mL (range: 15–65) and 25(OH)2D levels was 4.5 ng/mL (range: 25–80). Chest CT scan detected peripheral ground-glass opacity. Throat swab for coronavirus by RT-PCR assay tested positive for the virus. She was treated with lopinavir/ritonavir, third generation cephalosporin, anticoagulant, daily high-dose calcium acetate, vitamin D₃, fresh frozen plasma and oxygen therapy. She was discharged after two negative throat swab tests for coronavirus by conventional RT-PCR.

Learning points:

• Comorbidities are a risk factor for patients with COVID-19.

• Laboratory findings are unspecific in COVID-19 patients; laboratory abnormalities include lymphopenia, elevated of LDH, CPK and the inflammatory markers, such as C reactive protein, ferritinemia and the erythrocyte sedimentation rate.

• In addition to inflammatory markers, in COVID-19 patients it is crucial to check the level of vitamin D and calcium.

• There may be a correlation between vitamin D deficiency and the severity of COVID-19 disease.

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.

Summary

Autoimmune polyglandular syndrome type 1 (APS-1) is a very rare autoimmune entity, accounting for about 400 cases reported worldwide. It is characterized by the presence of at least two of three cardinal components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism and Addison’s disease. It typically manifests in childhood with CMC and years later with hypoparathyroidism. A 50-year-old man was referred to the Endocrinology outpatient clinic due to irregular follow-up of primary hypoparathyroidism diagnosed at age 7. Previous analysis reported frequent fluctuations of calcium and phosphate levels and persistent hypercalciuria. He presented several comorbidities, including bilateral cataracts, other ocular disorders, transient alopecia and chronic gastritis. Due to weight loss, fatigue, gastrointestinal complaints and the findings at objective examination, Addison’s disease and CMC were investigated and confirmed. Antifungal therapy and hormonal replacement were started with evident clinical improvement. Regarding hypoparathyroidism, calcium-phosphate product decreased and other extraskeletal calcifications were diagnosed, such as nephrolithiasis and in basal ganglia. Further evaluation by genetic analysis revealed homozygosity for a frameshift mutation considered to be a pathogenic variant. It was reported only in two Asian siblings in compound heterozygosity. This case highlights the broad phenotypic spectrum of APS-1 and the significative intra-familial phenotype variability. A complete clinical history taking and high index of suspicion allowed the diagnosis of this rare entity. This case clarifies the need for regular long-term follow-up. In the specific case of hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex.

Learning points:

• Autoimmune polyglandular syndrome type 1 (APS-1) is a deeply heterogeneous genetic entity with a broad spectrum of clinical manifestations and a significant intra-family phenotypic variability.

• Early diagnosis of APS-1 is challenging but clinically relevant, as endocrine and non-endocrine manifestations may occur during its natural history.

• APS-1 should be considered in cases of acquired hypoparathyroidism, and even more so with manifestations with early onset, family history and consanguinity.

• APS-1 diagnosis needs a high index of suspicion. Key information such as all the comorbidities and family aspects would never be valued in the absence of a complete clinical history taking.

• Especially in hypoparathyroidism and Addison’s disease in combination, the management of APS-1 can be complex and is not a matter of simply approaching individually each condition.

• Regular long-term monitoring of APS-1 is essential. Intercalary contact by phone calls benefits the control of the disease and the management of complications.

Summary

Despite improvements in localisation techniques and surgical advances, some patients with insulinoma will not be cured by surgery or may not be suitable for surgery. Medical management with diazoxide is an option for such cases. This case report details 27 years of successful management of insulinoma using diazoxide. It has been effective and safe, with only minor adverse effects.

Learning points:

• Long term diazoxide use can be a safe, effective option for insulinoma when it cannot be localised or removed surgically.

• Common adverse effects include peripheral oedema, hyperuricaemia, and hirsutism.

• ⁶⁸Ga-NOTA-exendin-4 PET/CT scan should be considered for insulinoma localisation when other modalities have been unhelpful.

Summary

Brown tumors are osteoclastic, benign lesions characterized by fibrotic stroma, intense vascularization and multinucleated giant cells. They are the terminal expression of the bone remodelling process occurring in advanced hyperparathyroidism. Nowadays, due to earlier diagnosis, primary hyperparathyroidism keeps few of the classical manifestations and brown tumors are definitely unexpected. Thus, it may happen that they are misdiagnosed as primary or metastatic bone cancer. Besides bone imaging, endocrine evaluation including measurement of serum parathyroid hormone and calcium (Ca) levels supports the pathologist to address the diagnosis. Herein, a case of multiple large brown tumors misdiagnosed as a non-treatable osteosarcoma is described, with special regards to diagnostic work-up. After selective parathyroidectomy, treatment with denosumab was initiated and a regular follow-up was established. The central role of multidisciplinary approach involving pathologist, endocrinologist and oncologist in the diagnostic and therapeutic work-up is reported. In our opinion, the discussion of this case would be functional especially for clinicians and pathologists not used to the differential diagnosis in uncommon bone disorders.

Learning points:

• Brown tumors develop during the remodelling process of bone in advanced and long-lasting primary or secondary hyperparathyroidism.

• Although rare, they should be considered during the challenging diagnostic work-up of giant cell lesions.

• Coexistence of high parathyroid hormone levels and hypercalcemia in primary hyperparathyroidism is crucial for the diagnosis.

• A detailed imaging study includes bone X-ray, bone scintiscan and total body CT; to rule out bone malignancy, evaluation of bone lesion biopsy should include immunostaining for neoplastic markers as H3G34W and Ki67 index.

• If primary hyperparathyroidism is confirmed, selective parathyroidectomy is the first-line treatment.

• In advanced bone disease, treatment with denosumab should be considered, ensuring a strict control of Ca levels.

Summary

Cushing’s syndrome is an endocrine disorder that causes anovulatory infertility secondary to hypercortisolism; therefore, pregnancy rarely occurs during its course. We present the case of a 24-year-old, 16-week pregnant female with a 10-month history of unintentional weight gain, dorsal gibbus, nonpruritic comedones, hirsutism and hair loss. Initial biochemical, hormonal and ultrasound investigations revealed hypokalemia, increased nocturnal cortisolemia and a right adrenal mass. The patient had persistent high blood pressure, hyperglycemia and hypercortisolemia. She was initially treated with antihypertensive medications and insulin therapy. Endogenous Cushing’s syndrome was confirmed by an abdominal MRI that demonstrated a right adrenal adenoma. The patient underwent right laparoscopic adrenalectomy and anatomopathological examination revealed an adrenal adenoma with areas of oncocytic changes. Finally, antihypertensive medication was progressively reduced and glycemic control and hypokalemia reversal were achieved. Long-term therapy consisted of low-dose daily prednisone. During follow-up, despite favorable outcomes regarding the patient’s Cushing’s syndrome, stillbirth was confirmed at 28 weeks of pregnancy. We discuss the importance of early diagnosis and treatment of Cushing’s syndrome to prevent severe maternal and fetal complications.

Learning points:

• Pregnancy can occur, though rarely, during the course of Cushing’s syndrome.

• Pregnancy is a transient physiological state of hypercortisolism and it must be differentiated from Cushing’s syndrome based on clinical manifestations and laboratory tests.

• The diagnosis of Cushing’s syndrome during pregnancy may be challenging, particularly in the second and third trimesters because of the changes in the maternal hypothalamic-pituitary-adrenal axis.

• Pregnancy during the course of Cushing’s syndrome is associated with severe maternal and fetal complications; therefore, its early diagnosis and treatment is critical.

Summary

Central diabetes insipidus (CDI) and several endocrine disorders previously classified as idiopathic are now considered to be of an autoimmune etiology. Dermatomyositis (DM), a rare autoimmune condition characterized by inflammatory myopathy and skin rashes, is also known to affect the gastrointestinal, pulmonary, and rarely the cardiac systems and the joints. The association of CDI and DM is extremely rare. After an extensive literature search and to the best of our knowledge this is the first reported case in literature, we report the case of a 36-year-old male with a history of CDI, who presented to the hospital’s endocrine outpatient clinic for evaluation of a 3-week history of progressive facial rash accompanied by weakness and aching of the muscles.

Learning points:

• Accurate biochemical diagnosis should always be followed by etiological investigation.

• This clinical entity usually constitutes a therapeutic challenge, often requiring a multidisciplinary approach for optimal outcome.

• Dermatomyositis is an important differential diagnosis in patients presenting with proximal muscle weakness.

• Associated autoimmune conditions should be considered while evaluating patients with dermatomyositis.

• Dermatomyositis can relapse at any stage, even following a very long period of remission.

• Maintenance immunosuppressive therapy should be carefully considered in these patients.

Summary

A 42-year-old man with complaints of muscle soreness and an increased pigmentation of the skin was referred because of a suspicion of adrenal insufficiency. His adrenocorticotropic hormone and cortisol levels indicated a primary adrenal insufficiency (PAI) and treatment with hydrocortisone and fludrocortisone was initiated. An etiological workup, including an assessment for anti-adrenal antibodies, very long-chain fatty acids, 17-OH progesterone levels and catecholamine secretion, showed no abnormalities. ¹⁸Fluorodeoxyglucose positron emission tomography/CT showed bilateral enlargement of the adrenal glands and bilateral presence of an adrenal nodule, with ¹⁸fluorodeoxyglucose accumulation. A positive tuberculin test and positive family history of tuberculosis were found, and tuberculostatic drugs were initiated. During the treatment with the tuberculostatic drugs the patient again developed complaints of adrenal insufficiency, due to insufficient dosage of hydrocortisone because of increased metabolism of hydrocortisone.

Learning points:

• Shrinkage of the adrenal nodules following tuberculostatic treatment supports adrenal tuberculosis being the common aetiology.

• The tuberculostatic drug rifampicin is a CYP3A4 inducer, increasing the metabolism of hydrocortisone. Increase the hydrocortisone dosage upon initiation of rifampicin in case of (adrenal) tuberculosis.

• A notification on the Addison’s emergency pass could be considered to heighten physician’s and patients awareness of hydrocortisone drug interactions.

Summary

A 26-year-old woman presented with persistent headache and tiredness. Biological investigations disclosed a moderate inflammatory syndrome, low PTH-hypercalcemia and complete anterior hypopituitarism. A magnetic resonance imaging (MRI) of the pituitary gland was performed and revealed a symmetric enlargement with a heterogeneous signal. Ophthalmological examination showed an asymptomatic bilateral anterior and posterior uveitis, and a diagnosis of pituitary sarcoidosis was suspected. As the localization of lymphadenopathies on the fused whole-body FDG-PET/computerized tomography (CT) was not evoking a sarcoidosis in first instance, an excisional biopsy of a left supraclavicular adenopathy was performed showing classic nodular sclerosis Hodgkin’s lymphoma (HL). A diagnostic transsphenoidal biopsy of the pituitary gland was proposed for accurate staging of the HL and surprisingly revealed typical granulomatous inflammation secondary to sarcoidosis, leading to the diagnosis of a sarcoidosis–lymphoma syndrome. The co-existence of these diseases constitutes a diagnostic challenge and we emphasize the necessity of exact staging of disease in order to prescribe adequate treatment.

Learning points:

• The possibility of a sarcoidosis–lymphoma syndrome, although rare, should be kept in mind during evaluation for lymphadenopathies.

• In the case of such association, lymphoma usually occurs after sarcoidosis. However, sarcoidosis and lymphoma can be detected simultaneously and development of sarcoidosis in a patient with previous lymphoma has also been reported.

• An accurate diagnosis of the disease and the respective organ involvements, including biopsy, is necessary in order to prescribe adequate treatment.

Learning points:

• CT is an unreliable method for distinguishing aldosterone-producing adenoma (APA) from bilateral adrenal hyperplasia (BAH).

• CT can be misleading in defining lateralisation of the aldosterone excess in case of unilateral disease (APA).

• AVS is the gold standard test for defining the PA subtype.