Autoimmunity, New Potential Biomarkers and the Thyroid Gland-The Perspective of Hashimoto's Thyroiditis and Its Treatment.

Autoimmune thyroid disease (AITD) is the most common organic specific illness of the thyroid gland. It may manifest as the overproduction or the decline of thyroxine and triiodothyronine. Hyperthyroidism develops due to the overproduction of hormones as an answer to the presence of stimulatory antibodies against the TSH receptor. Hashimoto's thyroiditis (HT) is generally characterized by the presence of thyroid peroxidase and thyroglobulin antibodies, with a concomitant infiltration of lymphocytes in the thyroid. Due to the progressive destruction of cells, AITD can lead to subclinical or overt hypothyroidism. Pathophysiology of AITD is extremely complicated and still not fully understood, with genetic, environmental and epigenetic factors involved in its development. Due to increasing incidence and social awareness of this pathology, there is an urgent need to expand the background concerning AITD. A growing body of evidence suggests possible ways of treatment apart from traditional approaches. Simultaneously, the role of potential new biomarkers in the diagnosis and monitoring of AITD has been highlighted recently, too. Therefore, we decided to review therapeutic trends in the course of AITD based on its pathophysiological mechanisms, mainly focusing on HT. Another aim was to summarize the state of knowledge regarding the role of new biomarkers in this condition.

Presenting symptoms and endocrine dysfunction in Rathke cleft cysts - a two-centre experience.

INTRODUCTION: Rathke cleft cysts (RCC) arise as developmental abnormalities of the pituitary gland and are usually diagnosed incidentally. However, they may present with headaches, visual impairment, or pituitary dysfunction. Rathke cleft cysts are poorly described in the Polish literature. We aimed to characterize presenting symptoms, associated endocrine dysfunction, and concomitant disorders in the Polish population of patients with RCC. MATERIAL AND METHODS: We performed a retrospective analysis of medical records of 102 patients diagnosed with RCC between 2006 and 2021 at Heliodor Swiecicki Clinical Hospital in Poznan and Independent Public Clinical Hospital No. 4 in Lublin. RESULTS: The cohort was 72% female, with a mean age of 43 years. The median maximal cyst diameter was 7 mm. The majority of subjects were overweight or obese and presented lipid profile or glucose disturbances. Common presenting symptoms included headache, vertigo, and visual impairment. Less frequently we observed sexual dysfunction, irregular menses, galactorrhoea, or fatigue. Hormonal abnormalities were identified in 30% of patients, with hyperprolactinaemia being the commonest endocrinopathy (23%). Pituitary function in patients with RCC did not correlate with cyst size. Both concomitant pituitary adenomas and pineal cysts were diagnosed in 3% of patients. A considerable proportion of subjects were diagnosed with Hashimoto's thyroiditis and multinodular goitre. CONCLUSIONS: RCCs occur mostly in females and may result in a variety of symptoms and hormonal dysfunction. Patients require a full clinical and endocrine evaluation regardless of the cyst diameter. We report a substantial co-occurrence of RCC and metabolic disorders and primary thyroid diseases, which requires further investigation.

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab?

The aim of the study was to assess the occurrence and nature of immune-related endocrine adverse events (irAEs) among patients with non-small-cell lung cancer (NSCLC) treated with nivolumab. METHODS: The study group included 35 patients (15 women, 20 men, 65.8 ± 7.1 years) with NSCLC in stage IIIB (n = 16, 45.7%) and IV (n = 19,54.3%) who were treated with nivolumab. RESULTS: Of the studied patients, 34.3% (n = 12) developed endocrine irAEs (irAE group): 22.9% (n = 8) hyperthyroidism and 8.6% (n = 3) hypothyroidism, and in one case, hypophysitis was observed. The median irAEs onset time was 2 months. In the group of patients with thyroid disorders, permanent hypothyroidism eventually developed in 58.3%. The severity of the analyzed irAEs ranged from mild to moderate (Grade 1-2); the case of hypophysitis was estimated as Grade 3. The comparison of progression-free survival time (PFS) between the two groups showed longer PFS in patients in the irAE group (p = 0.021). Patients with irAE were treated significantly longer with nivolumab and they received more doses of nivolumab, however in Cox analysis we did not find patients with irAE to experience progression later than patients without them. CONCLUSIONS: Nivolumab therapy is associated with an increased risk of endocrine adverse effects, particularly thyroid dysfunction. Endocrine adverse effects can be successfully treated pharmacologically and usually do not require discontinuation of immunotherapy. The relationship between a better cancer prognosis in patients who developed endocrine irAE has not been found.

Pancreatic neuroendocrine tumours in patients with von Hippel-Lindau disease.

Von Hippel-Lindau disease is a highly penetrant autosomal genetic disorder caused by a germline mutation in the tumour suppressor gene, manifesting with the formation of various tumours, including neuroendocrine tumours of the pancreas. The incidence of the latter is not very high, varying from 5% to 18%. To compare, haemangioblastomas and clear cell renal carcinoma are present in 70% of von Hippel-Lindau patients and are considered the main prognostic factors, with renal cancer being the most common cause of death. However, pancreatic neuroendocrine tumours should not be neglected, considering their malignant potential (different to sporadic cases), natural history, and treatment protocol. This paper aims to review the literature on the epidemiology, natural history, treatment, and surveillance of individuals affected by pancreatic neuroendocrine tumours in von Hippel-Lindau disease.

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients-Literature Review.

In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on the surface of T lymphocytes may be stimulated via a specific PD-ligand 1 (PD-L1), which inhibits lymphocyte activation and leads to apoptosis. Some malignant cells are characterized by high PD-L1 expression. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with non-small cell lung cancer (NSCLC), it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3-23%). Thyroid disorders are the most common, with severity rarely exceeding grade 2. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. Individuals with autoimmune diseases diagnosed prior to immunotherapy are at risk of its exacerbation. In the management of patients receiving immunotherapy, evaluation of history of autoimmune diseases, awareness and early diagnosis of irAE are crucial and may affect treatment outcomes.

Gestational diabetes mellitus - literature review on selected cytokines and hormones of confirmed or possible role in its pathogenesis.

The incidence of gestational diabetes mellitus (GDM) increases globally, including Poland. Considering serious consequences of gestational diabetes for both mother and fetus, screening for this disorder is an obligatory element of managing pregnant woman. The pathogenesis of gestational diabetes is not yet thoroughly explained. However, it is insulin resistance and chronic subclinical inflammatory process which are considered to be major factors responsible for the development of GDM. These two states are triggered mainly by secretion of proinflammatory cytokines and by abnormal function of adipose tissue. The study reviews the literature on selected hormones and cytokines whose role in the GDM pathogenesis has been already confirmed as well as on those proteins whose role is either not yet fully understood or which may possibly participate in GDM development. Owing to the fact that underlying mechanisms of GDM are, in general, similar to the mechanisms responsible for metabolic disorders such as diabetes mellitus type 2 or obesity, in this review we focus first on the role these molecules play in pathogenesis of metabolic disorders and then present current state of knowledge on their action in gestational diabetes development. The review presents: TNF alpha, adipokines - adiponectin and leptin and relatively newly discovered proteins: fetuin A, periostin, angiopoietin-like protein 8 or high mobility group box.

Familial isolated pituitary adenomas (FIPA). Case report of four families and review of literature.

Background The majority of pituitary adenomas are sporadic, but about 5% of them occur in a familial setting, predominantly in multiple endocrine neoplasia type 1 and Carney complex. Familial isolated pituitary adenomas (FIPA), unrelated to the syndromes mentioned above, were also described. The clinical course of FIPA differs significantly from sporadic cases, and is characterized by a larger tumor size, more aggressive course and younger patients' age at the moment of recognition. Objectives The aim of this retrospective study is to present 4 families in which two closely related people were diagnosed with pituitary adenomas. Probably these cases are clinical manifestations of FIPA. Material and methods Eight patients within four families, presenting with anterior pituitary tumors were described. The authors analyzed medical and family histories of the patients, their imaging pictures (pituitary MRI/CT) and hormonal tests. Results Family 1.: two sisters with acromegaly in the course of macroadenoma. Family 2.: two brothers with clinically nonsecreting macroadenomas. Family 3.: father and daughter with clinically nonsecreting macroadenomas. Family 4.: young man with acromegaly caused by macroadenoma and a daughter of his mother`s sister with microprolactinoma. CONCLUSIONS: Familial isolated pituitary adenomas are more common than it was previously thought, therefore, specific questioning regarding family history should be a part of the workup of all patients with pituitary adenomas. Genetically induced pituitary tumors often have aggressive behavior in terms of tumor expansion and resistance to different treatment options and often involve a multidisciplinary approach that combines endocrine, neurosurgical, and radiological specialists.

Perioperative complications of gynecologic surgery in diabetic patients.

OBJECTIVES: The aim of the study was to estimate whether diabetes was an independent risk factor for perioperative complications in patients undergoing gynecologic surgery. MATERIAL AND METHODS: The study population consisted of 182 women (diabetics and controls) who underwent elective gynecologic surgery. Each patient without diabetes from the control group and matched for age and body mass index diabetic patient were admitted with the same gynecologic diagnosis, underwent the same gynecologic procedure, were operated on in the same operating room and were hospitalized within the same time interval. The following parameters of the perioperative period were compared between every matched pair of patients (diabetic vs. non-diabetic patient): number and characteristics of intra- and postoperative complications, length of postoperative hospitalization, decrease in hemoglobin level, increase in body temperature, and postoperative use of antibiotics. RESULTS: The study revealed no statistically significant differences between the diabetic patients and pair-matched controls in terms of the examined parameters of the perioperative period. CONCLUSIONS: Diabetes was not an independent risk factor for early postoperative complications after gynecologic procedures in the examined population. Good pre-operative glycemic control and strict cooperation of the diabetologist with the surgeon in the perioperative period resulted in reduction of the complication rate to the level typical for non-diabetic patients.

Catecholamine crisis as a first manifestation of familial bilateral pheochromocytoma caused by RET proto-oncogene mutation in codon C 634R.

INTRODUCTION: Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disorder caused by mutation in the RET proto-oncogene. MEN 2A includes medullary carcinoma of the thyroid, pheochromocytoma, and primary hyperparathyroidism. The authors present a case study of three family members with bilateral pheochromocytoma in the course of MEN 2A, a catecholamine crisis being the first manifestation of the syndrome in one of them. Case 1: A 30-year-old man without a history of hypertension or any other chronic medical problems was admitted to the Emergency Department because of a hypertensive crisis that was followed by cardiac arrest. A later diagnosis revealed bilateral pheochromocytoma and RET proto-oncogene mutation in codon 634. The patient underwent bilateral adrenalectomy and total thyroidectomy; the latter confirmed the presence of medullary carcinoma. Case 2: The patient underwent right adrenalectomy with the removal of a pheochromocytoma at the age of sixteen. Ten years later, a suspicion of pheochromocytoma in the remaining left adrenal was raised. Mutation in the RET proto-oncogene was confirmed as well. The patient first underwent left adrenalectomy and then she had total thyroidectomy. Postoperative histopathological examinations revealed pheochromocytoma and medullary carcinoma. Case 3: Radiological and biochemical examination confirmed pheochromocytoma. Therefore, the two adrenals were removed. As mutation in codon 634 was detected, the patient underwent total thyroidectomy as well. The presence of medullary carcinoma was confirmed. CONCLUSIONS: Pheochromocytoma is a rare and potentially lethal disease if a catecholamine crisis develops. Its recognition requires further investigation towards genetic syndromes, particularly MEN 2A.

Familial acromegaly - case study of two sisters with acromegaly.

In the majority of cases, acromegaly is sporadic. However, it can also occur in a familial setting as a component of MEN-1, MEN-4, Carney complex (CNC) or as the extremely rare syndrome of isolated familial somatotropinoma (IFS), the latter belonging to familial isolated pituitary adenomas (FIPA). The diagnosis of IFS is based on the recognition of acromegaly/gigantism in at least two family members, given that the family is not affected by MEN-1, MEN-4 or CNC. The authors present a case study of two sisters: a 56 year-old patient (case no. 1) and a 61 year-old patient (case no. 2). In both sisters, acromegaly was recognised in the course of pituitary macroadenoma. Neither of the sisters showed features of MEN-1, MEN-4 or Carney complex. The authors suppose that the presented cases are manifestations of IFS. However, this diagnosis has not been confirmed yet because of the poor availability of genetic tests.