Summary

Primary hyperparathyroidism requires a surgical approach to achieve a long-term cure. However, post-surgical recurrence significantly complicates the management of this condition. A number of causes for recurrent disease are well understood and several diagnostic modalities exist to localise the culprit parathyroid adenoma although none of them is efficacious in localisation of the recurrent lesion. In this case report, we highlight a novel causative mechanism and describe a unique diagnostic sequence that enabled curative treatment to be delivered.

Learning points

• In the case described herein, we describe a novel location for a parathyroid adenoma causing recurrent PHPT. The case elucidates well the difficulties presented by such cases in terms of surgical planning and show the utility of PVS in such cases. Based on this case, we make the following recommendations:

• Meticulous care must be taken to prevent seeding of adenomatous tissue during primary excision.

• To consider the use of PVS in patients with discordant imaging in the setting of recurrent/persistent PHPT as a method to localise the causative adenoma.

• Same day PVS and surgery is a viable option for patients who either represent an anaesthetic risk or who are extremely anxious about the prospect of two separate procedures.

• Disordered calcium homeostasis is an important but forgotten cause of dysphagia which can be extremely debilitating for affected patients.

Summary

Berardinelli–Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive disease, characterized by the absence of subcutaneous adipose tissue, leptin deficiency and severe metabolic complications, such as insulin resistance, diabetes mellitus, and dyslipidemia. The most common mutation occurs in BCSL2 which encodes seipin, a protein involved in adipogenesis. We report a patient with BSCL who was diagnosed with diabetes at 11 years old. He was started on metformin 1000 mg twice daily, which lowered glycated hemoglobin (HbA1c) to less than 7%. Four months later, HbA1c raised above 7.5%, indicating secondary failure to metformin. Therefore, we added the peroxisome proliferator-activated receptor-gamma (PPARG) agonist, pioglitazone. Since then and for the last 5 years his HbA1c has been within the normal range. These findings indicate that pioglitazone should be considered as a valid alternative in the treatment of diabetes in BSCL patients. To the best of our knowledge, this is the first specific report of successful long-term treatment with pioglitazone in a patient with BSCL.

Learning points

• Berardinelli–Seip congenital lipodystrophy (BSCL) is a recessive genetic disorder associated with severe insulin resistance and early onset diabetes, usually around puberty. Failure of oral antidiabetic medication occurs within the first years of treatment in BSCL patients.

• When failure to achieve metabolic control with metformin occurs, pioglitazone may be a safe option, lowering insulin resistance and improving both the metabolic control and lipodystrophic phenotype.

• Herein we show that pioglitazone can be a safe and efficient alternative in the long-term treatment of BSCL patients with diabetes.

Summary

Apart from adrenal myelolipomas, adrenal lipomatous tumors are rare and only seldom described in the literature. We present the case of a 50-year-old man, with a classical form of congenital adrenal hyperplasia (CAH), which was well treated with prednisolone and fludrocortisone. The patient presented with pollakisuria and shortness of breath while bending over. On MRI, fat-equivalent masses were found in the abdomen (14 × 19 × 11 cm on the right side and 10 × 11 × 6 cm on the left side). The right adrenal mass was resected during open laparotomy and the pathohistological examination revealed the diagnosis of an adrenal lipoma. Symptoms were subdued totally postoperatively. This is the first report of a bilateral adrenal lipoma in a patient with CAH that we are aware of.

Learning points:

• Macronodular hyperplasia is common in patients with congenital adrenal hyperplasia (CAH).

• Solitary adrenal tumors appear in approximately 10% of adult CAH patients and are often benign myelolipomas.

• The Endocrine Society Clinical Practice Guideline does not recommend routine adrenal imaging in adult CAH patients.

• Adrenal imaging should be performed in CAH patients with clinical signs for an adrenal or abdominal mass.

• Adrenal lipoma is rare and histopathological examinations should rule out a differentiated liposarcoma.

Summary

Succinate dehydrogenase deficiency has been associated with several neoplasias, including renal cell carcinoma (RCC) and those associated with hereditary paraganglioma (PGL)/ pheochromocytoma (PHEO) syndromes, Carney dyad, and Carney triad. Carney triad is a rare multitumoral syndrome characterized by co-existing PGL, gastrointestinal stromal tumor (GIST), and pulmonary chondroma (CHO). We report a case of a 57-year-old male who presented with para-aortic and gastroesophogeal masses, and a right renal superior pole lesion, which were classified as multiple PGLs, a GIST, and a clear cell renal carcinoma, respectively, on pathology following surgical resection. Additionally, a CHO was diagnosed radiologically, although no biopsy was performed. A diagnosis of Carney triad was made. SDHB immunohistochemical staining was negative for the PGL and the GIST, indicating SDH-deficiency. Interestingly, the renal cell carcinoma (RCC) stained positive for both SDHB and SDHA. Subsequent genetic screening of SDH subunit genes revealed a germline inactivating heterozygous SDHA pathogenic variant (c.91 C>T, p.R31X). Loss of heterozygosity was not detected at the tumor level for the RCC, which likely indicated the SDHA variant would not be causative of the RCC, but could still predispose to the development of neoplasias. To the knowledge of the authors this is the first reported case of an SDHA pathogenic variant in a patient with Carney triad complicated by RCC.

Learning points

• The succinate dehydrogenase enzyme is encoded by four subunit genes (SDHA, SDHB, SDHC, and SDHD; collectively referred to as SDHx), which have been implicated in several neoplasias and are classified as tumor suppressor genes.

• Carney triad is a rare multiple-neoplasia syndrome presenting as an association of PGLs, GISTs, and CHOs.

• Carney triad is most commonly associated with hypermethylation of SDHC as demonstrated in tumor tissue, but approximately 10% of cases are due to pathogenic SDHx variants.

• Although SDHB pathogenic variants are most commonly reported in SDH-deficient renal cell carcinoma, SDHA disease-causing variants have been reported in rare cases.

Learning points:

• The c.57delG SDHD mutation may confer a more aggressive phenotype than other mutations associated with familial paraganglioma syndrome type 1.

• A capillary hemangioma, a component of other pseudohypoxia states, was observed in the lung of a single member of the c.57delG SDHD kindred.

• This report supports the hypothesis of others that mutations found near the beginning of the SDHD open reading frame are more likely to demonstrate an aggressive phenotype.

Summary

A 26-year-old Caucasian female with no past medical history or family history of auto-immune disease presented to the emergency department with new onset painless left foot drop. A panel of blood tests revealed blood glucose of 49.9 mmol/L and raised blood ketone levels. The patient was referred to the diabetes team who made a clinical diagnosis of type 1 diabetes (T1DM) and insulin treatment was initiated. Elevated levels of diabetes auto-antibodies were subsequently detected. Nerve conduction studies demonstrated a left common peroneal nerve lesion with conduction block at the fibular head. After 2 weeks of insulin treatment, a significant improvement of her foot drop was observed and after 8 weeks she was walking normally. The most probable cause of her foot drop was acute diabetic mononeuropathy. To our knowledge, there are no similar cases in adult patients reported in the literature. Our case highlights the importance of physicians being aware of atypical presentation of new onset T1DM.

Learning points:

• There is an increasing incidence of T1DM with more than half of patients presenting after the age of 20.

• Diabetic peripheral neuropathy can present both acutely and as a mononeuropathy.

• Although rare, clinicians should be aware of mononeuropathy as a presenting symptom of T1DM to avoid delay in the treatment initiation.

• This case highlights an unusual presentation of T1DM and illustrates the importance of the early diagnosis and management of T1DM.

Learning points:

• Sotos syndrome is a disorder of childhood overgrowth caused by NSD1 deletions.

• Duplications involving NSD1 cause a ‘reverse Sotos syndrome’ phenotype characterised by short stature and microcephaly.

• The contrasting phenotypes of NSD1 deletions and duplications suggest a dose effect.

• Stimulated growth hormone secretion is normal in children with NSD1 deletions and duplications.

• Growth hormone therapy can be very effective in children with NSD1 duplications, comparable to the response seen in severe growth hormone deficiency.

Summary

Struma ovarii is a teratoma of the ovaries predominantly composed of thyroid tissue. Hyperthyroidism associated with struma ovarii is rare, occurring in approximately 8% of cases. Due to the rarity of struma ovarii, available data are limited to case reports and small case series.We report on a 61-year-old female patient with known Hashimoto’s thyroiditis on levothyroxine replacement therapy for years with transition to clinical and biochemical hyperthyroidism despite antithyroid medication with carbimazole (10 mg/day), new diagnosis of urothelial carcinoma and an adnexal mass suspicious of ovarian cancer. The patient underwent resection of the adnexal mass and histopathology revealed a mature teratoma predominantly composed of thyroid tissue showing high levels of sodium iodide symporter protein expression. Following struma ovarii resection and disappearance of autonomous production of thyroid hormones, the patient developed hypothyroidism with severely decreased thyroid hormone levels fT4 and fT3 (fT4 0.4 ng/dL, reference interval 0.9–1.7 and fT3 < 1.0 pg/mL, reference interval 2.0–4.4). This has previously been masked by continued thyroid-stimulating hormone suppression due to long-term hyperthyroidism pre-surgery indicating secondary hypothyroidism, in addition to primary hypothyroidism based on the known co-existing chronic lymphocytic thyroiditis of the orthotopic thyroid gland. Levothyroxine administration was started immediately restoring euthyroidism.This case illustrates possible diagnostic pitfalls in a patient with two concurrent causes of abnormal thyroid function.

Learning points:

• Struma ovarii is an ovarian tumor containing either entirely or predominantly thyroid tissue and accounts for approximately 5% of all ovarian teratomas.

• In rare cases, both benign and malignant struma ovarii can secrete thyroid hormones, causing clinical and biochemical features of hyperthyroidism.

• Biochemical features of patients with struma ovarii and hyperthyroidism are similar to those of patients with primary hyperthyroidism. In such cases, thyroid scintigraphy should reveal low or absent radioiodine uptake in the thyroid gland, but the presence of radioiodine uptake in the pelvis in a whole body radioiodine scintigraphy.

• We give advice on possible diagnostic pitfalls in a case with two simultaneous causes of abnormal thyroid function due to the co-existence of struma ovarii.

Summary

Whilst literature is expanding on pasireotide use in the management of Cushing’s disease (CD), there is still currently much unknown about long-term and low-dose pasireotide use in CD. We present a 60-year-old female with residual CD after transphenoidal surgery (TSS), being successfully managed with S.C. pasireotide for over 10 years. For 6 years, her S.C. pasireotide was inadvertently administered at 360 µg twice daily (BID), almost half the recommended dose of 600 µg BID. Despite the low-dose, her urinary free cortisol (UFC) normalised within 6 months and Cushingoid features resolved. She remained in biochemical and clinical remission on the same low-dose for 6 years, before a medication audit discovered her mistaken dose and directed her to take 600 µg BID. With the higher dose 600 µg BID for the next 5 years, her glycaemia worsened without any changes in her UFC and residual tumour volume. Our case showed the continuing effectiveness and safety of treatment with S.C. pasireotide for more than 10 years, and that a low-dose regimen may be considered an option for responders by its safety profile.

Learning points:

• A lower dose of pasireotide may be effective in the initial treatment of CD than the recommended 600 µg BID dosage, though more studies are required to explore this.

• Low-dose pasireotide use has the benefit of minimising adverse effects.

• In the long-term, pasireotide has a sustained clinical and biochemical effect and is well tolerated.

Summary

Pituitary metastasis (PM) can be the initial presentation of an otherwise unknown malignancy. As PM has no clinical or radiological pathognomonic features, diagnosis is challenging. The authors describe the case of a symptomatic PM that revealed a primary lung adenocarcinoma. A 62-year-old woman with multiple sclerosis and no history of malignancy, incidentally presented with a diffusely enlarged and homogeneously enhancing pituitary gland associated with stalk enlargement. Clinical and biochemical evaluation revealed anterior hypopituitarism and diabetes insipidus. Hypophysitis was considered the most likely diagnosis. However, rapid visual deterioration and pituitary growth raised the suspicion of metastatic involvement. A search for systemic malignancy was performed, and CT revealed a lung mass, which proved to be a lung adenocarcinoma. Accordingly, the patient was started on immunotherapy. Resection of the pituitary lesion was performed, and histopathology analysis revealed metastatic lung adenocarcinoma. Following surgery, the patient underwent radiotherapy. More than 2 years after PM detection, the patient shows a clinically relevant response to antineoplastic therapy and no evidence of PM recurrence.

Learning points:

• Although rare, metastatic involvement of the pituitary gland has been reported with increasing frequency during the last decades.

• Pituitary metastasis can be the initial presentation of an otherwise unknown malignancy and should be considered in the differential diagnosis of pituitary lesions, irrespective of a history of malignancy.

• The sudden onset and rapid progression of visual or endocrine dysfunction from a pituitary lesion should strongly raise the suspicion of metastatic disease.

• MRI features of pituitary metastasis can overlap with those of other pituitary lesions, including hypophysitis; however, rapid pituitary growth is highly suggestive of metastatic disease.

• Survival after pituitary metastasis detection has improved over time, encouraging individualized interventions directed to metastasis to improve quality of life and increase survival.