Summary

We present two cases of thyroid sarcoidosis that were misdiagnosed as thyroid cancer. In the first patient, fine needle aspiration cytology (FNAc) of a suspicious thyroid nodule indicated the presence of papillary thyroid cancer, and the patient underwent thyroid surgery. However, histopathology identified a sarcoid granuloma, without any sign of malignancy. The second patient had a history of papillary microcarcinoma with suspicious lymph nodes diagnosed years after the initial diagnosis and was referred for assessment of cervical lymphadenopathy. Fine needle aspiration cytology (FNAc) of the suspicious lymph nodes erroneously indicated metastasis from thyroid cancer, and lateral modified lymph node dissection was performed, based on FNAc and ultrasonographic features. Histopathology excluded malignancy and identified non-caseating granulomas. Sarcoidosis of the thyroid may have a clinical presentation similar to well-differentiated thyroid carcinoma and, although rare, should be considered in the differential diagnosis, especially when other signs of the disease are already present. In these cases, FNAc provided a false diagnosis of papillary thyroid carcinoma and lymph node metastases that led to unnecessary surgery.

Learning points

• Sarcoidosis may share clinical and ultrasonographic features with papillary thyroid carcinoma.

• Fine needle aspiration cytology is helpful in the diagnosis of both conditions; however, the overlapping cytological characteristics may lead to erroneous diagnosis.

• The present cases illustrate the importance of cytological identification of these difficult cases. Every piece of information provided by the clinician is essential to the cytologist.

Summary

Factitious Cushing’s syndrome (CS) is a very rare form of Münchausen syndrome. Its presentation and course are extremely heterogeneous, and diagnosis is generally challenging. We report the case of a 52-year-old woman who was initially investigated because of the occurrence of cushingoid features. Nevertheless, endocrine work-up showed very low morning plasma ACTH and serum cortisol levels. In addition, it also demonstrated central hypopituitarism and hypogonadotropic hypogonadism. Head MRI showed a small pituitary mass. Based on these results, and probably overlooking the initial clinical suspicion, general practitioner (GP) referred the patient to our Endocrine Unit for hypopituitarism. At inspection, moon face, central obesity, and bruising were evident. Multiple ulcerative skin lesions were also concentrated in the right arm and leg. Dermatology evaluation suggested that the lesions were self-provoked. For several days, the patient denied the assumption of corticosteroids, but we finally discovered that the GP’ nurse had prescribed betamethasone without the GP’s knowledge for about 2 years. In conclusion, the surreptitious assumption of corticosteroids is very rare, but the physicians should be aware that pituitary function could be impaired by high doses of corticosteroids, mimicking hypopituitarism. In these patients, a multidisciplinary approach and environmental investigation can be useful to diagnose factitious CS.

Learning points

• Surreptitious assumption of corticosteroids can cause heterogeneous presentation, ranging from Cushing’s syndrome to multiple hypopituitarism.

• Suppression of ACTH and cortisol levels in a patient with cushingoid features firstly suggests surreptitious assumption of corticosteroids.

• A multidisciplinary approach can be extremely useful in patients with suspected factitious Cushing’s syndrome.

• Sometimes, to prove surreptitious assumption of corticosteroids needs environmental investigation.

Summary

We present a 54-year-old patient admitted to the emergency department due to loss of consciousness. The initial ECG registered monomorphic ventricular extrasystoles and prolonged QT interval (QT corrected (QTc) >500 ms). Sustained ventricular tachycardia (VT) was registered on 24-h Holter ECG monitoring, which clinically was presented as a crisis of consciousness. Coronary angiography and other visualization methods were normal. Implantable cardioverter-defibrillator (ICD) implantation was planned for the purpose of secondary prevention of sudden cardiac death (SCD). Laboratory and hormonal analyzes revealed primary hyperparathyroidism (PHPT), chronic kidney disease, and hypokalemia. Neck ultrasound showed a 25 mm, sharply outlined homogenous tumor mass which was separated from thyroid gland (TG) and exerted a mild impression on lower parts of the left lobe. Dual wash technetium-99m sestamibi parathyroid scintigraphy with single-photon emission CT (SPECT)/CT also showed the uptake of tracer behind the lower half of the left lobe of the TG. Surgical treatment, lower left parathyroidectomy, was performed, and pathohistological analysis verified parathyroid adenoma. The patient was rhythmically and hemodynamically stable for 7 days after surgery, without additional complaints, and was discharged from the hospital. Timely diagnosis of PHPT, correct assessment and surgical treatment, did not lead our patient to unnecessary ICD implantation. Our case suggests an additional intertwining of electrolyte disorders and ventricular arrhythmias in PHPT and more importantly emphasizes the need for caution when indicating ICD, even in patients with the most serious life-threatening arrhythmias.

Learning points

• Electrolyte abnormalities in PHPT can have highly malignant consequences, and the occurrence of hypokalemia in the presence of hypercalcemia is underestimated in PHPT, and the consequences can be life-threatening.

• Although hypercalcemia causes shortened QT interval, concomitant severe hypokalemia may overcome hypercalcemia and prolong QT interval, even in the absence of structural heart disease or LQTS.

• Timely diagnosis of PHPT, correct assessment and surgical treatment, do not lead to unnecessary ICD implantation.

Summary

Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, approved for the treatment of type 2 diabetes mellitus (T2DM). GLP-1 analogs exert several biological activities connected not only with an insulinotropic effect but also with immunoregulation and reduction of inflammation. A 73-year-old male patient with class III obesity was referred to us for T2DM, which was not controlled with metformin therapy. He had suffered from plaque psoriasis for some years and was treated with topical therapy and adalimumab, without success. The psoriasis area and severity index (PASI) was 33.2 (indicating severe psoriasis), and the dermatology life quality index (DLQI) was 26.0 (indicating an extremely negative effect on the patient's life). Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 12 weeks, and then to 1 mg/week) was added to metformin. After 4 months, glycemic parameters had improved, and his body weight decreased. Unexpectedly, skin lesions of plaque psoriasis improved. PASI decreased by 19% compared with baseline and quality of life, assessed with the DLQI, markedly ameliorated. After 10 months, glycemic and obesity parameters, as well as psoriasis, improved further. HbA1c, BMI, and PASI were reduced by 32, 16.3, and 92%, respectively, compared with the baseline. DLQI declined to 0, meaning there was no effect of plaque psoriasis on the patient’s life.

Learning points

• Psoriasis in patients with type 2 diabetes is often resistant to therapy.

• We observed an obese patient with type 2 diabetes mellitus who achieved glycemic control and weight loss with the addition of semaglutide to metformin and had a relevant and long-lasting improvement of plaque psoriasis, which was previously resistant to biologic therapy.

• Therapy with semaglutide may be attempted in eligible patients with difficult to treat plaque psoriasis.

Summary

Acute respiratory distress syndrome (ARDS) is a rare but life-threatening complication of diabetic ketoacidosis (DKA). We present the case of a young female, with no previous diagnosis of diabetes, presenting in DKA complicated by ARDS requiring extra corporeal membrane oxygenation (ECMO) ventilator support. This case report highlights the importance of early recognition of respiratory complications of severe DKA and their appropriate management.

Learning points

• ARDS is a very rare but life-threatening complication in DKA.

• The incidence of ARDS remains unknown but less frequent than cerebral oedema in DKA.

• The mechanism of ARDS in DKA has multifactorial aetiology, including genetic predisposition.

• Early recognition and consideration of rare pulmonary complication of DKA can increase survival rate and provide very satisfactory outcomes.

• DKA patients who present with refractory ARDS can be successfully rescued by ECMO support.

Summary

Carbimazole is a commonly used antithyroid drug (ATD), which is associated with several well-established side effects. However, Carbimazole-induced rhabdomyolysis is rarely reported in the literature. We report a 27-year-old male who presented with upper limb myalgia and significantly raised creatine kinase elevation, 1-month post commencement of Carbimazole for Graves’ disease. Carbimazole was ceased with subsequent clinical and biochemical improvement. Though the pathophysiology remains unclear, we hope to raise awareness regarding this rare adverse effect with a view to promote early recognition and prompt discontinuation of the offending medication caused by a commonly used medication in endocrinology.

Learning points

• Musculoskeletal complaints can relate to unidentified and untreated hyperthyroidism. However one must be mindful that the treatment for these disorders can too induce myopathies.

• ATD-induced myopathy should be considered when there is a temporal relationship between introduction of ATDs and the onset of symptoms.

• If ATD-induced myopathy is being considered, other causes of myopathy should still be outruled.

• Prompt discontinuation of potentially offending medications may provide resolution of symptoms and avoid significant consequences.

Summary

We present the case of a 45-year-old Caucasian woman who attended the Endocrinology Unit for a left cervical mass discovered during follow-up for autoimmune chronic thyroiditis. The ultrasound-guided fine-needle aspiration biopsy of the lesion was consistent with a metastasis of follicular thyroid carcinoma. The sonographic neck evaluation revealed no thyroid nodules but three markedly hypoechoic and highly vascularized areas, with irregular margins and hyperechoic spots. In the clinical suspicion of primary thyroid neoplasm, ultrasound-guided fine-needle aspiration biopsy of two of the three areas was performed, but both cytological reports were non-diagnostic, revealing only colloid and blood. Subsequently, the patient underwent surgical removal of the cervical mass, with the intra-operatory consultation with frozen section examination suggesting follicular-like neoplasia. For this reason, thyroidectomy with both central and lateral neck dissection was performed. Surprisingly, the final histologic examination revealed chronic thyroiditis in the thyroid specimen and no evidence of metastasis in the left neck mass. Consequently, the pathological revision of the frozen section assessment led to the final diagnosis of chronic thyroiditis on the lateral ectopic thyroid. This case represents an uncommon example of lateral ectopic thyroid tissue with coexisting normally located thyroid tissue both affected by chronic thyroiditis.

Learning points

• Ectopic thyroid must be considered in the diagnostic work-up of lateral neck mass.

• Even if rare, ectopic thyroid tissue can be found lateral to the carotid sheath and with coexisting normally located thyroid tissue.

• As the orthotopic tissue, lateral ectopic thyroid tissue can be affected by chronic thyroiditis, which may complicate the diagnosis both on ultrasound and cytology.

Summary

During pregnancy, maternal tissues become increasingly insensitive to insulin in order to liberate nutritional supply to the growing fetus, but occasionally insulin resistance in pregnancy becomes severe and the treatment challenging. We report a rare and clinically difficult case of extreme insulin resistance with daily insulin requirements of 1420 IU/day during pregnancy in an obese 36-year-old woman with type 2 diabetes (T2D) and polycystic ovary syndrome (PCOS). The woman was referred to the outpatient clinic at gestational week 12 + 2 with a hemoglobin A1c (HbA1c) at 59 mmol/mol. Insulin treatment was initiated immediately using Novomix 30, and the doses were progressively increased, peaking at 1420 units/day at week 34 + 4. At week 35 + 0, there was an abrupt fall in insulin requirements, but with no signs of placental insufficiency. At week 36 + 1 a, healthy baby with no hypoglycemia was delivered by cesarean section. Blood samples were taken late in pregnancy to search for causes of extreme insulin resistance and showed high levels of C-peptide, proinsulin, insulin-like growth factor (IGF-1), mannan-binding-lectin (MBL) and leptin. CRP was mildly elevated, but otherwise, levels of inflammatory markers were normal. Insulin antibodies were undetectable, and no mutations in the insulin receptor (INSR) gene were found. The explanation for the severe insulin resistance, in this case, can be ascribed to PCOS, obesity, profound weight gain, hyperleptinemia and inactivity. This is the first case of extreme insulin resistance during pregnancy, with insulin requirements close to 1500 IU/day with a successful outcome, illustrating the importance of a close interdisciplinary collaboration between patient, obstetricians and endocrinologists.

Learning points

• This is the first case of extreme insulin resistance during pregnancy, with insulin requirements of up to 1420 IU/day with a successful outcome without significant fetal macrosomia and hypoglycemia.

• Obesity, PCOS, T2D and high levels of leptin and IGF-1 are predictors of severe insulin resistance in pregnancy.

• A close collaboration between patient, obstetricians and endocrinologists is crucial for tailoring the best possible treatment for pregnant women with diabetes, beneficial for both the mother and her child.

Summary

Insulin autoimmune syndrome (IAS) is a rare cause of non-islet cell hypoglycaemia. Treatment of this condition is complex and typically involves long-term use of glucocorticoids. Immunotherapy may provide an alternative in the management of this autoimmune condition through the suppression of antibodies production by B-lymphocyte depletion. We present a case of a 62-year-old male, with refractory hypoglycaemia initially presenting with hypoglycaemic seizure during an admission for acute psychosis. Biochemical testing revealed hypoglycaemia with an inappropriately elevated insulin and C-peptide level and no evidence of exogenous use of insulin or sulphonylurea. Polyethylene glycol precipitation demonstrated persistently elevated free insulin levels. This was accompanied by markedly elevated anti-insulin antibody (IA) titres. Imaging included CT with contrast, MRI, pancreatic endoscopic ultrasound and Ga 68-DOTATATE position emission tomography (DOTATATE PET) scan did not reveal islet cell aetiology for hyperinsulinaemia. Maintenance of euglycaemia was dependent on oral steroids and dextrose infusion. Complete resolution of hypoglycaemia and dependence on glucose and steroids was only achieved following treatment with plasma exchange and rituximab.

Learning points

• Insulin autoimmune syndrome (IAS) should be considered in patients with recurrent hyperinsulinaemic hypoglycaemia in whom exogenous insulin administration and islet cell pathologies have been excluded.

• Biochemical techniques play an essential role in establishing high insulin concentration, insulin antibody titres, and eliminating biochemical interference. High insulin antibody concentration can lead to inappropriately elevated serum insulin levels leading to hypoglycaemia.

• Plasma exchange and B-lymphocyte depletion with rituximab and immunosuppression with high dose glucocorticoids are effective in reducing serum insulin levels and hypoglycaemia in insulin autoimmune syndrome (IAS).

• Based on our observation, the reduction in serum insulin level may be a better indicator of treatment efficacy compared to anti-insulin antibody (IA) titre as it demonstrated greater correlation to the frequency of hypoglycaemia and to hypoglycaemia resolution.

Summary

Although pituitary macroadenomas often cause mass effects on surrounding structures, it is extremely rare for pituitary lesions to disturb cerebrospinal fluid circulation. Sellar gangliocytoma-pituitary adenomas (SGPAs) are also extremely rare. Here we report the unique case of a man with the unusual combination of acromegaly from an SGPA, who presented with unilateral hydrocephalus. A 60-year-old man presented with rapid neurological deterioration, bitemporal hemianopia, and acromegalic features. Neuroimaging revealed a large sellar lesion extending superiorly into the left foramen of Monro, causing acute obstructive unilateral hydrocephalus. External ventricular drain placement improved consciousness immediately. Biochemical assessment confirmed acromegaly. Following trans-sphenoidal debulking, histology revealed a mixed gangliocytoma/sparsely-granulated somatotrophinoma. Despite the residual disease, his vision recovered remarkably, low-dose cabergoline controlled residual excess growth hormone (GH) secretion, and the residual tumour has remained extremely stable over 2 years. Hydrocephalus is an extremely rare complication of pituitary lesions, and unilateral hydrocephalus has never been reported previously. GH secretion in SGPAs is more common than for pituitary adenomas in general, raising questions regarding the aetiology and therapeutic approach to this rare combination tumour.

Learning points

• Pituitary tumours most commonly present with symptoms related to endocrine disturbance or mass effects upon visual pathways (e.g. optic chiasm, nerves in the lateral cavernous sinus). However, extremely rarely, pituitary masses may disrupt cerebrospinal fluid (CSF) circulation resulting in hydrocephalus.

• Sellar gangliocytomas are very rare tumours and most of them are hybrid tumours with pituitary adenomas (SGPAs).

• SGPAs are typically indolent and may be functioning or non-functioning tumours.

• Growth hormone (GH)-producing SGPAs are less likely to respond to somatostatin agonists than classic somatotrophinomas.

• Primary surgical debulking via a trans-sphenoidal approach was effective in this individual, leading to the restoration of CSF circulation and improvement in visual disturbance, while also negating the need for permanent CSF diversion despite the residual tumour burden.