Summary

Calciphylaxis is a rare disorder characterised by the development of painful necrotic skin lesions. Occlusion of cutaneous arterioles due to ectopic calcification leads to potentially life-threatening widespread skin loss. Most cases occur in patients with chronic renal disease, which leads to dysregulation of calcium and phosphate homeostasis. Only a handful of case reports exist describing calciphylaxis occurring in patients without chronic renal disease but with hypoparathyroidism. We report on a unique case of a 53-year-old man with multiple endocrine neoplasia type 1 syndrome and acquired hypoparathyroidism due to total parathyroidectomy who went on to develop calciphylaxis following cardiac surgery.

Learning points

• Calciphylaxis most commonly occurs in the context of chronic renal disease but can rarely occur in its absence as a consequence of calcium and phosphate dysregulation.

• Patients who develop necrotic skin lesions in the presence of hypoparathyroidism require an urgent dermatological opinion.

• Mortality from calciphylaxis is high, with the majority of deaths occurring secondary to sepsis.

• Management of calciphylaxis requires a multidisciplinary team approach to manage wound healing, infections and pain.

• Recovery with full rehabilitation from calciphylaxis can take months to years.

Summary

We report a case of catamenial erythema multiforme major in a 46-year-old female. She was treated successfully with goserelin, a GnRH agonist, until the expected age of menopause; however, its therapeutic effects persisted for longer than expected, possibly due to accumulation in adipose tissue.

Learning points

• A group of menstrual cycle-related dermatoses and hypersensitivity syndromes exist but are rarely reported in the literature.

• A history of recurrent cutaneous eruptions in premenopausal females should be considered in the context of the menstrual cycle.

• The diagnosis of menstrual cycle-related dermatoses is largely clinical, although provocation testing can assist.

• Treatment options are broad and are aimed at reducing the immune response and/or suppressing ovulation.

• Goserelin may accumulate and have a gonadotrophin-suppressing effect for longer than expected.

Summary

Mitotane is used for treatment of advanced adrenocortical carcinoma. It is administered when the carcinoma is unresectable, metastasized, or at high-risk of recurrence after resection. In addition, mitotane is considered to have direct adrenolytic effects. Because of its narrow therapeutic–toxic range, therapeutic drug monitoring (TDM) is warranted. In 2020, a left-sided adrenal gland tumor was found (5.8 cm) in a 38-year-old man. Considering the size of this lesion and inability to exclude an adrenocortical carcinoma on imaging, a laparoscopic adrenalectomy was performed. Histopathologic examination determined presence of an adrenocortical carcinoma (pT2N0M0 ENSAT stadium II; ki67 10–15%). There was no evidence for residual or metastatic disease but given the high risk of recurrence, adjuvant therapy with mitotane was initiated. During TDM, a sudden and spuriously high level of mitotane was observed but without signs or symptoms of toxicity. After exploration, it was found that this high concentration was completely due to uncontrolled hypertriglyceridemia. After correction thereof, mitotane levels were again in the therapeutic range. This observation underscores the importance of TDM sampling in a fasting state with concurrent control of prevalent or incident dyslipidemia.

Learning points

• TDM of mitotane is advocated to achieve therapeutic levels while avoiding toxicity. For correct TDM, sampling should be done at least 12 h after last intake of mitotane.

• Although sampling in fasting conditions in not explicitly mentioned in the guidelines, fasting state should be considered as elevated serum triglyceride levels might cause spuriously high mitotane levels.

• In patients undergoing treatment with mitotane and presenting with too high or unexplained fluctuating mitotane levels without signs or symptoms of toxicity, hypertriglyceridemia as a possible cause should be investigated.

• If dyslipidemia occurs in patients under mitotane treatment, other causes than mitotane (e.g. alcohol abuse and diabetes) should be considered and appropriate treatment should be initiated.

Summary

With rising rates of adoption and surrogacy, induced lactation is likely to become increasingly relevant, allowing women who did not undergo pregnancy to breastfeed. We describe the case of a woman with complete androgen insensitivity syndrome (CAIS) on conventional oestrogen therapy who was expecting a child via surrogacy and who wished to breastfeed. The woman was commenced on supplementary oestrogen therapy, domperidone and breast stimulation by mechanical breast pump 8 weeks prior to the delivery of her child. Following delivery, the patient produced a small, unquantified amount of milk, allowing her to suckle the infant for a short period of time. Induced lactation is possible in chromosomally XY individuals. It has been most successful in cis-women and transwomen, both of whom have had progesterone/progestogen exposure to the breast. We suggest that the addition of a progestogen to our patient’s treatment regimen, either as part of her original hormone therapy or part of the lactation induction program, would have improved her changes of establishing successful lactation.

Learning points

• Induced lactation is possible in chromosomally XY individuals with the use of pharmacological and non-pharmacological therapies.

• There are no standardised guidelines regarding the optimal regimen for induced lactation.

• Progesterone exposure to the breast is essential for ductal branching and alveolar maturation.

• In the published literature, induced lactation is more successful in transwomen and other XY individuals who have had prior progesterone exposure.

• The addition of progestogen to our patient’s treatment regimen would have improved her chances of establishing successful lactation.

Summary

We present a young woman with treatment resistant insulin autoimmune syndrome (IAS) with a protracted course. Her serum insulin level was 6945 pmol/l (<160), C-peptide 4042 pmol/L (<1480), anti-insulin antibodies 5305 U/mL (<0.4) were monoclonal IgG kappa. After 12 h of fasting, her blood glucose fell to 1.2 mmol/L. Post-meal blood glucose peaked at 12.2 mmol/L with reactive hypoglycaemia below 2 mmol/L. Frequent meals and continuous blood glucose monitoring were helpful, but further treatments advocated in the literature with prednisolone, rituximab, plasmapheresis, cyclophosphamide and ciclosporin were without beneficial effect.

Based on this case and a review of the literature, we propose that IAS is not one but two different diseases with different therapeutic strategies. The first disease, polyclonal IAS, predominates in Asia and is characterized by polyclonal anti-insulin antibodies, association with certain HLA genotypes and other autoimmune conditions, medications and viral infections possibly triggering the disease, a possible female predominance among young patients and a tendency towards spontaneous remission. The other disease, monoclonal IAS, predominates in Caucasians. Typical features are monoclonal anti-insulin antibodies, only weak HLA association, no drug predisposition, no sex difference, rare remission and conventional therapy often being without any clinical effect. We suggest that monoclonal IAS with IgG or IgA anti-insulin antibodies should receive therapy targeting plasma cells rather than lymphocytes.

Learning points

• IAS may be considered as two separate diseases, polyclonal and monoclonal.

• The presence of either polyclonal or monoclonal antibodies should determine the choice of treatment for IAS.

• In polyclonal IAS, discontinuation of a triggering medication and treatment of triggering conditions should be the backbone of therapy.

• Monoclonal IAS should receive treatment targeting plasma cells.

Summary

In patients with diabetes mellitus, the toxic milieu caused by abnormal glucose and free fatty acid handling can lead to heart failure (HF). Referred to as diabetic cardiomyopathy (DMCM), this syndrome often exists in the absence of conventional risk factors for HF such as history of myocardial infarction or hypertension. Low-carbohydrate diets (LCDs) have recently been endorsed as an efficacious therapeutic dietary approach to prevent and reverse cardiometabolic disease including type 2 diabetes mellitus (T2DM). LCDs improve systemic insulin resistance (IR), reverses cardiac remodelling in a rodent model and downregulates the expression of sodium–glucose co-transporter 2 (SGLT2) receptors in the kidney. It is therefore conceivable that a lifestyle approach such as adopting an LCD can be offered to patients with DMCM. The reported case is that of a 45-year-old man with a 15-year history of non-ischaemic cardiomyopathy, T2DM and obesity. The patient volunteered to engage in a 16-week low-carbohydrate dietary intervention trial and then self-selected to remain on this diet for 1 year. The whole-food LCD was based on simple ‘traffic light’ style food lists and not designed to restrict calories, protein, fat or salt. After 1 year, the patient had lost 39 kg and his cardiometabolic markers had significantly improved. LCDs present a potentially beneficial approach for patients with DMCM and could be considered as a lifestyle intervention before SGLT2i therapy is commenced.

Learning points

• Diabetic cardiomyopathy (DMCM) is a syndrome precipitated mainly by the detrimental effects of glucose metabolism disorders such as insulin resistance and diabetes.

• Low-carbohydrate diets (LCD) mimic many effects of sodium–glucose co-transporter 2 inhibitors (SGLT2i).

• LCDs are a dietary pattern which can have significant and beneficial effects on metabolic and anthropometric markers in patients with DMCM.

• LCDs and SGLT2i therapy could be combined and may achieve better clinical outcomes for patients with DMCM.

• Combination therapy may be carried out under close supervision as the real risk for diabetic ketoacidosis remains.

Summary

Primary hyperparathyroidism most commonly presents with hypercalcaemia. Rarely, parathyroid apoplexy or haemorrhage mimicking a thyroid bleeding cyst is the first presentation of a parathyroid adenoma. A woman presented with a sudden-onset painful ‘goitre’. Ultrasound showed a cystic nodule located posterior to rather than in the right thyroid lobe, suggesting parathyroid adenoma bleeding. Biochemistry showed mild primary hyperparathyroidism. ^99mTc-pertechnetate/sestamibi showed no uptake in the nodule, which was interpreted as a cold thyroid nodule. ¹⁸F-fluorocholine PET/CT showed uptake in the nodule, suggestive of a parathyroid adenoma. Persistent mild primary hyperparathyroidism complicated by nephrolithiasis and osteopenia favoured parathyroidectomy over a wait-and-see approach. The patient was referred for parathyroidectomy along with right thyroid lobectomy. Pathology showed an adenoma, with an eccentrically located cystic structure filled with red blood cells surrounded by a thickened fibrous capsule. In conclusion, cervical pain/haemorrhage with hypercalcaemia points to the diagnosis of parathyroid apoplexy, mimicking a thyroid bleeding cyst. Workup with ultrasound and, if available, ¹⁸F-choline PET/CT allows for timely surgery, minimizing the risk of recurrent and severe bleeding.

Learning points

• A bleeding cyst may be located posterior to rather than in the thyroid, suggesting a parathyroid haemorrhage.

• Neck pain and/or haemorrhage along with primary hyperparathyroidism point to parathyroid apoplexy.

• A two-step presentation has been described, with a first phase of local symptoms to be followed by visible and possibly life-threatening compressing bleeding.

• Therefore, an expedited workup is needed, allowing for timely surgery.

Summary

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the destruction of the pancreatic beta cells, which produce insulin. Individuals with T1DM usually require at least 3-5 years to develop microvascular complications in comparison to people with type 2 diabetes (T2DM), who may develop complications even before the diagnosis of diabetes. We discuss a patient who presented with proliferative diabetic retinopathy subsequently diagnosed with T1DM and diabetic neuropathy following investigations. Diabetic retinopathy or other microvascular complications as the presenting feature of T1DM is rarely known or reported in the literature. A 33-year-old healthcare worker had been seen by the opticians due to 1-week history of blurred vision. The ophthalmology assessment had confirmed proliferative retinopathy in the right eye and severe non-proliferative retinopathy in the left eye with bilateral clinically significant macular oedema. His BMI was 24.9 kg/m². The nervous system examination revealed bilateral stocking type peripheral neuropathy. The random venous glucose was 24.9 mmol/L. Plasma ketones were 0.7 mmol/L and HbA1c was 137 mmol/mol. On further evaluation, the anti-glutamic acid decarboxylase (GAD) antibody was positive, confirming the diagnosis of T1DM. He was started on aflibercept injections in both eyes, followed by panretinal photocoagulation. Subsequent nerve conduction studies confirmed the presence of symmetrical polyneuropathy. The pathogenesis of the development of microvascular complications in T1DM is multifactorial. Usually, the development of complications is seen at least a few years following the diagnosis. The occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important in preventing the progression of the disease.

Learning points

• The pathogenesis of the development of microvascular complications in type 1 diabetes mellitus is multifactorial.

• The development of complications is seen at least a few years following the diagnosis.

• Occurrence of microvascular complications at presentation is rare.

• This makes the management challenging and extremely important to prevent the progression of the disease.

Summary

Severe Cushing’s syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare but often demands rapid diagnostics and treatment of hypercortisolism with its comorbidities. Pharmacotherapy of hypercortisolism by ketoconazole, metyrapone and osilodrostat is currently available. If unsuccessful or insufficient a bilateral adrenalectomy is an option. We present a 28-year-old female with severe Cushing’s syndrome caused by a bronchial metastatic neuroendocrine tumour (NET). Hypercortisolism was efficiently treated by osilodrostat with block–replace and then titration regimen. A once-daily dose was finally used with normalised cortisol levels. Androgen levels measured by liquid chromatography–mass spectrometry were slightly elevated during the treatment but without any symptoms. A simple once-daily use of osilodrostat with titration regimen led to normalised cortisol levels in a severe Cushing’s syndrome patient with an uncurable bronchial NET. Transient hypocortisolism during treatment appeared but was easily treated by hydrocortisone.

Learning points

• Cushing’s syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare.

• Cortisol upregulation is often severe and rapid, though clinical signs are not always fully pronounced.

• Rapid treatment is a key for preventing and reducing complications such as fractures, thromboembolism, bleeding, hyperglycaemia, and arterial hypertension.

• The novel potent steroidogenesis inhibitor osilodrostat can be used as first-line treatment for reducing hypercortisolism.

Summary

We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case.

Learning points

• Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival.

• PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome.

• Brain metastasis although rare indicate aggressive phenotypic features.

• Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.