Distinct clinical picture of Cushing's syndrome in a patient with Morris' syndrome - first literature report.

Not required for Clinical Vignette.

Does nesfatin-1 influence the hypothalamic-pituitary-gonadal axis in adult males with obstructive sleep apnoea?

There is growing evidence that obstructive sleep apnoea (OSA) influences the hypothalamic-pituitary-gonadal axis (HPG axis) in men. The aim of the study was to assess the association of nesfatin-1 with HPG axis disturbances in OSA. This is a prospective study with consecutive enrolment. It comprises 72 newly diagnosed OSA patients ((AHI: apnoea-hypopnea index) 18 subjects: 5 ≤ AHI < 15; 24: 15 ≤ AHI < 30; 30: AHI ≥ 30) and a control group composed of 19 patients (AHI < 5). All patients underwent polysomnography and fasting blood collection for nesfatin-1, testosterone, luteinising hormone (LH), high-sensitivity C-reactive protein (hsCRP), aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine and glucose. Groups had similar levels of LH, nesfatin-1 and testosterone (p = 0.87; p = 0.24; p = 0.08). Nesfatin-1 was not correlated to LH (p = 0.71), testosterone (p = 0.38), AHI (p = 0.34) or the oxygen desaturation index (ODI) (p = 0.69) either in the whole group, or in sub-groups. The study did not reveal any association between the HPG axis and nesfatin-1 in OSA adult males. It is possible that nesfatin-1 is not a mediator of HPG axis disturbances in adult patients with OSA.

Malignancy Risk and Hormonal Activity of Adrenal Incidentalomas in a Large Cohort of Patients from a Single Tertiary Reference Center.

BACKGROUND: A rise in adrenal incidentalomas (AIs) detection has been observed recently. Even though AIs are detected in asymptomatic patients, thorough assessment may reveal hormonal and metabolic abnormalities or malignant character. METHODS: Medical records of 2005 patients (1301 women, 704 men) with 2498 tumors aged 61 ± 11.3 (18-93) years, who had been hospitalized due to AI diagnosis, were reviewed. Patients underwent clinical examination, adrenal CT and hormonal assessment. In patients subjected to adrenalectomy, histopathological character of AI was confirmed. RESULTS: AIs most frequently occurred in patients in their 7th decade of life. Hypertension was present in 76.6%, glucose metabolism disorders in 41.3%, and hypercholesterolemia in 60.1% of patients. Lipid-rich adenomas (83.2%) and hormonally inactive tumors (83.1%) predominated. Autonomous cortisol secretion was present or suspected in 6.6%, pheochromocytoma in 4.7%, hyperandrogenism in 3.1%, and primary hyperaldosteronism in 2.4% of patients. The risk of malignancy increased in patients with tumors >6 cm was 37.7%. The logistic regression analysis revealed that the strongest predictor of hormonal activity of AIs was lipid-poor picture on CT scan (OR 7.072; CI 5.118-9.771), while the most important factor increasing the risk of malignancy was lipid-poor adenoma or non-adenoma on CT scan (OR 4.843; CI 1.697-13.819). Final histopathology was available for 214 tumors; 106 adrenocortical adenomas, 46 pheochromocytomas, and 18 adrenocortical carcinomas were diagnosed. CONCLUSION: Most AIs are hormonally inactive adenomas. The most frequent hormonal manifestation of AI is subclinical hypercortisolemia. Presence of AI is often accompanied by features of metabolic syndrome. The tumor density on CT scan picture may be predictive of both hormonal activity and the risk of malignancy. Tumors of all sizes may exhibit hormonal activity, while the risk of malignancy significantly increases with the size above 6 cm.

An adult female with headache and bilateral shank ache.

Not required for Clinical Vignette.

The role of immunohistochemical examination in diagnosis of papillary thyroid cancer in struma ovarii.

INTRODUCTION: Struma ovarii (SO) is a monodermal teratoma in which thyroid tissue comprises more than 50% of the tumour. Papillary thyroid cancer (PTC) in SO is a rare finding, as only 5% of SO cases undergo malignant transformation. Malignant SO is usually asymptomatic and infrequently diagnosed preoperatively. Because of its rarity, there is no consensus about diagnosis and management, while treatment and follow-up procedures are not clearly established. MATERIAL AND METHODS: Herewith, we report two cases of PTC in SO. The first patient was a 25-year-old woman diagnosed with bilateral ovarian tumours. The second patient, 19-year-old woman, presented with unilateral ovarian mass. Both patients were qualified for surgical excision of the tumours. Histopathological specimens underwent both conventional histopathological assessment and immunohistochemical staining. RESULTS: In the first patient histopathology revealed SO with two foci of PTC. Immunohistochemically a positive expression of CK7, CK19, p63 and thyroglobulin (Tg) confirmed the diagnosis. She underwent total thyroidectomy in 2016 in order to enable ablative radioiodine therapy and facilitate further thyroglobulin monitoring. Unfortunately, the patient was lost from follow-up. In the second patient, histopathological diagnosis was follicular variant of PTC in SO. Postoperatively, a pelvic CT revealed osteolytic lesion 6 cm in size, being a metastatic change. The patient underwent unilateral ovariectomy, total thyroidectomy and multiple cycles of radioiodine therapy. Currently, 9 years following the diagnosis, the patient achieved disease remission. CONCLUSIONS: PTC in SO still remains a diagnostic and therapeutic challenge. Immunostaining for CK7, CK19, p63 and Tg might be helpful in histopathological diagnosis. The decision on the need of total thyroidectomy and radioiodine therapy should be made individually. However, thyroid remnant ablation increases the sensitivity and specificity of follow-up testing using serum Tg level as a tumour marker.

Severe unilateral orbitopathy in a patient with Hashimoto's thyroiditis - a case report.

BACKGROUND: Thyroid-associated orbitopathy (TAO) constitutes an immune-mediated inflammation of the orbital tissues of unclear etiopathogenesis. TAO is most prevalent in hyperthyroid patients with Graves' disease (GD); however, severe cases of orbitopathy associated with Hashimoto's thyroiditis (HT) have rarely been described. CASE PRESENTATION: Herewith we report an unusual case of a middle-aged clinically and biochemically euthyroid woman with a stable HT, who developed a severe unilateral left-sided TAO. Thyrotropin receptor antibodies (TRAb) concentration was negative. Intraocular pressure in the left eye was mildly elevated (24 mmHg), while vision acuity was not compromised. Abnormal positioning of the eyeball suggested the extraocular muscles involvement. Unilaterally, von Graefe's, Stellwag's, Kocher's and Moebius' signs were positive. Conjunctival erythema, redness and edema of the eyelid and an enlarged, swollen lacrimal caruncle were visible. She received 4/7 points in the Clinical Activity Scale (CAS) and class IV in the NO SPECS severity scale for the left eye (I-0, II-a, III-0, IV-b, V-0, VI-0). Magnetic resonance imaging (MRI) revealed thickening of the left medial rectus muscle with an increase in T2 signal intensity and prolonged T2 relaxation indicating an active form of TAO. The patient received therapy with glucocorticosteroids intravenously, followed by intramuscular injections with a cumulative dose of 3.24 g of methylprednisolone during a 9-week period with good tolerance. The applied therapy, combined with adequate L-thyroxine substitution, as well as vitamin D and selenium supplementation, resulted in a complete remission of ophthalmic symptoms. CONCLUSIONS: Unilateral exophthalmos in TRAb-negative patients with HT is not a typical manifestation of the disease, and requires a wider differential diagnosis with MRI of the orbits. Scheme of three iv. pulses of methylprednisolone intravenously and the continuation of treatment with im. injections seems to be an effective and safe method of treatment in this group of patients. What is more, adequate vitamin D supplementation and the maintenance of biochemical euthyroidism may help to achieve an ultimate therapeutic effect. Patients with TAO in the course of HT need a careful and continued interdisciplinary approach both ophthalmological and endocrinological. Further studies are needed to elucidate the etiopathogenesis of TAO in TRAb-negative patients.

Primary pigmented nodular adrenocortical disease (PPNAD) as an underlying cause of symptoms in a patient presenting with hirsutism and secondary amenorrhea: case report and literature review.

Hypercortisolemia in females may lead to menstrual cycle disturbances, infertility, hirsutism and acne. Herewith, we present a 18-year-old patient, who was diagnosed due to weight gain, secondary amenorrhea, slowly progressing hirsutism, acne and hot flashes. Thorough diagnostics lead to a conclusion, that the symptoms was the first manifestation of primary pigmented nodular adrenocortical disease (PPNAD). All symptoms of Cushing syndrome including hirsutism and menstrual disturbances resolved after bilateral adrenalectomy. Our report indicates that oligo- or amenorrhea, hirsutism, acne in combination with weight gain, growth failure, hypertension and slightly expressed cushingoid features in a young woman requires diagnostics towards hypercortisolemia. Despite PPNAD is a very rare cause of ACTH-independent Cushing syndrome, it has to be taken into consideration, especially when adrenal glands appear to be normal on imaging and paradoxical rise in cortisol level in high-dose dexamethasone test is observed. Unlike in our patient, in vast majority of patients, PPNAD is associated with Carney complex (CC). Therefore, these patients and their first-degree relatives should be always carefully screened for symptoms of PPNAD, CC and genetic mutations of PRKAR1A, PDE11A, and PDE8B genes.

Association between bone remodeling and inflammatory markers in obstructive sleep apnea in relation to disease severity.

INTRODUCTION    There is growing evidence that obstructive sleep apnea (OSA) influences both bone metabolism and structure. Chitinase­3­like protein 1 (YKL­40) is a novel inflammatory and remodeling marker, the levels of which were shown to increase in OSA. YKL­40 can probably alter the bone turnover. OBJECTIVES    The aim of the study was to assess a possible interplay between YKL­40 and bone turnover markers in patients with different stages of OSA, and to evaluate the relation between bone mass, severity of OSA, and YKL­40 levels. PATIENTS AND METHODS    The study involved 72 male patients with OSA. They were divided into 3 groups according to disease severity, using the apnea-hypopnea index (AHI): group 1 (n = 18; 5≤ AHI <15), group 2 (n = 25; 15≤ AHI <30), and group 3 (n = 29; AHI ≥30). All patients underwent polysomnography and densitometry. Fasting blood samples were collected for YKL­40, C­terminal telopeptide of typeI collagen (CTX), procollagen type 1 N­terminal propeptide (P1NP), and other markers. RESULTS    P1NP differed between groups 1 and 2, as well as groups 1 and 3 (P = 0.02). Group 2 had higher CTX levels than group 1 (borderline significance, P = 0.05). A simple linear regression analysis showed that serum YKL­40 levels were associated with the levels of CTX (P <0.0001, ß = 0.9871) and P1NP (P <0.0001, ß = 0.9780). CONCLUSIONS    Our study might suggest that YKL­40 is associated with bone turnover in OSA. We may assume that this marker influences both bone formation and destruction; thus, OSA could be characterized by preserved bone mineral density.

Obstructive sleep apnea and hormones - a novel insight.

Obstructive sleep apnea (OSA), a disorder characterized by repetitive collapse of the upper respiratory tract during sleep, occurs in about 4% of middle-aged men and 2% of women. The incidence of the disorder is rising due to an increase in obesity and ageing of the population. Patients with obstructive sleep apnea are at elevated risk of some endocrinal and metabolic disorders, which may lead to serious consequences including shortening of life expectancy. The recognition and understanding of interactions between local upper airway dysfunction and its endocrinal consequences is therefore vital. In this review we will focus on the influence of OSA on bone metabolism and endocrine homeostasis.

Diagnostic pitfalls of adrenal incidentaloma.

Adrenal incidentaloma (AI) includes all lesions with diameter ≥ 1 cm found incidentally during imaging examinations not associated with suspected adrenal pathology. Every adrenal incidentaloma requires a detailed hormonal and imaging assessment. Initial diagnosis includes radiological phenotypical evaluation (particularly in CT, or in case of contraindications - in MRI) and biochemical assessment of tumour hormonal activity (which includes cortisol circadian rhythm, salivary cortisol concentration, 24-hour urinary free-cortisol and metanephrines test, short cortisol and dexamethasone suppression test, ACTH level assessment, aldosterone and ARO concentration, adrenal androgen concentration). Each diagnostic step is associated with limitations and method imperfections. The influence of administered medications, age and concomitant diseases must be taken into account when interpreting test results. It is important to remember abovementioned factors may cause false positive or false negative test results. The following paper is to summarize the etiology of the most common diagnostic mishaps which frequently lead to misdiagnoses, an increase in patient's anxiety and, as a consequence, in the introduction of improper therapy or its discontinuation. The awareness of biochemical and imaging test limitations, and the knowledge of false positive and false negative result sources, allows for the optimisation of the diagnostic process. Simultaneously, the analyzed factors may contribute to a decrease in unnecessary and frequently repeated tests. Additionally, it may imply avoiding the costs of unjustified deep diagnostics.