Enterohepatic circulation of triiodothyronine

The major factor regulating thyroid function is thyroid stimulating hormone (TSH), a glycoprotein released by the thyrotropic cells of the pituitary gland. Determinants of the TSH secretion rate are inhibition by thyroxine (T 4), 3, 3', 5-triiodothyronine (T3), dopamine, glucocorticoids and somatostatin, and stimulation by TSH-releasing hormone (TRH), (nor)adrenaline and perhaps neurotensin [156]. In the control of thyroid hormone bioavailability, an important role is also played by iodothyronine transport into cells, enzymatic deiodination and conjugation. Several groups have studied the enterohepatic metabolic pathways of iodothyronines. It has been generally accepted that these pathways have no more than a passive function in the elimination of the hormone. However, if enterohepatic circulation (EHC) of iodothyronines occurs, the intestinal tract may constitute an important pool of exchangeable hormone. Until recently, only few and inconclusive data existed concerning this EHC. In our studies we have attempted to document the possible existence of an EHC of thyroid hormone and the role it may play in regulating overall hormone metabolism and excretion in the rat. Especially, we wanted to assess the importance of the intestinal microflora for this process. We have studied the biliary clearance of T3 and its conjugates, the hydrolysis of iodothyronine conjugates by intestinal bacteria and intestinal contents, and the metabolism of T3 and its conjugates in conventional (CV) and intestine-decontaminated (ID) rats. It is the purpose of this thesis to discuss the role of the EHC of iodothyronines in thyroid hormone metabolism, with special emphasis on the results of my own studies of this subject, described in detail in the appendix papers

Van Docter Bernardo naar Endocriene Weesaandoeningen

Rede, uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar met als leeropdracht Endocriene oncologie aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 24 november 201

Clémentine Delait (1865–1934), the most famous bearded lady on the continent in the 20th century

Clémentine Delait Clattaux (1865–1934), the Bearded Woman from Thaon-les-Vosges, France, did not suffer from her extreme hirsutism, but used it to her advantage. Her beard started to grow when she turned 18 and at the age of 25 she decided to stop shaving her beard and let it grow. She had regular menstrual cycles between ages 12 and 35. She was diagnosed with signs and symptoms of hyperandrogenism like hirsutism, impressive strength and muscularity and a deep voice, but also with morbid obesity. She never gave birth to a child. At the age of 39, she was officially allowed by the French Government to wear man’s clothes. She suffered from rheumatism and died because of a stroke. The most probable cause of her hirsutism was polycystic ovary syndrome. Alternatively, an incomplete block in the adrenal steroid synthesis, like nonclassical 21-hydroxylase deficiency can be considered

The Evolution of Neuroendocrine Tumor Treatment Reflected by ENETS Guidelines

In 2016, the third version of guidelines for the diagnosis and treatment of neuroendocrine tumors (NETs) has been published by the European Neuroendocrine Tumor Society (ENETS). These guidelines reflect the progress in treatment of NETs, and by comparing the newest guidelines with the first guidelines of 2001, this progress can be clearly recognized. Diagnostic accuracy has been increased by the introduction of PET-CT with Ga-labelled somatostatin analogs, and multiple new treatments and treatment schedules have been developed, like peptide receptor radiotherapy with radiolabeled somatostatin analogs, or targeted therapies. Evidence and indications for these therapi

Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms

Neuroendocrine neoplasms constitute a diverse group of tumors that derive from the sensory and secretory neuroendocrine cells and predominantly arise within the pulmonary and gastrointestinal tracts. The majority of these neoplasms have a well-differentiated grade and are termed neuroendocrine tumors (NETs). This subgroup is characterized by limited proliferation and patients affected by these tumors carry a good to moderate prognosis. A substantial subset of patients presenting with a NET suffer from the consequences of endocrine syndromes as a result of the excessive secretion of amines or peptide hormones, which can impair their quality of life and prognosis. Over the past 15 years, critical developments in tumor grading, diagnostic biomarkers, radionuclide imaging, randomized controlled drug trials, evidence-based guidelines, and superior prognostic outcomes have substantially altered the field of NET care. Here, we review the relevant advances to clinical practice that have significantly upgraded our approach to NET patients, both in diagnostic and in therapeutic options

Medical treatment of Cushing's syndrome: Adrenal-blocking drugs and ketaconazole

Cushing's syndrome is associated with serious morbidity and increased mortality. Irrespective of its cause, i.e. a pituitary adenoma, ectopic ACTH production or an adrenal neoplasia, Cushing's syndrome is primarily treated surgically. However, when surgery is unsuccessful or contraindicated, medical therapy is needed to treat hypercortisolism. The spectrum of available drugs includes adrenal-blocking agents, neuromodulatory drugs and glucocorticoid receptor antagonists. Adrenal blocking drugs suppress adrenal cortisol production via inhibition of steroidogenic enzymes. Ketoconazole and metyrapone are most frequently used for this purpose, but chronic treatment with these drugs can be limited by side effects like hepatotoxicity (ketoconazole) and increased androgen and mineralocorticoid production (metyrapone). Etomidate can be used to rapidly reverse cortisol excess in patients with acute complications of (severe) hypercortisolism like psychosis. In Cushing's disease, combination therapy with drugs that target the corticotropic adenoma, i.e. the universal somatostatin analogue pasireotide and/or the dopamine agonist cabergoline, and low-dose ketoconazole seems a rational approach to achieve biochemical control

Considerations concerning a tailored, individualized therapeutic management of patients with (neuro)endocrine tumours of the gastrointestinal tract a

Endocrine tumours of the gastrointestinal tract and pancreas may present at different disease stages with either hormonal or hormone-related symptoms/syndromes, or without hormonal symptoms. They may occur either sporadically or as part of hereditary syndromes. In the therapeutic approach to a patient with these tumours, excessive hormonal secretion and/or its effects should always be controlled first. Tumour-related deficiencies or disorders should also be corrected. Subsequently, control should be aimed at the tumour growth. Surgery is generally considered as first-line therapy for patients with localized disease, as it can be curative. However, in patients with metastatic disease the role of first-line surgery is not clearly established and other therapies should be considered, such as non-surgical cytoreductive therapies, biotherapy (with somatostatin analogues or interferon-alpha), embolization and chemoembolization of liver metastases, chemotherapy (with single or multiple dose regimens) and peptide receptor-targeted radiotherapy. The delicate balance of the use of the different therapeutical options in patients with endocrine tumours of the gastrointestinal tract and pancreas emphasizes the importance of team approach and team expertise

Pituitary adenomas, some diagnostic and therapeutical aspects

The treatment of almost all types of pituitary adenomas has changed considerably in recent years. New types of drugs as well as improved application forms of older drug therapies are now becoming more and more available for everyday treatment of patients with these relatively rare diseases. For the most frequently occurring pituitary adenomas the drugs of first choice are described, as well as other available treatments, their indications and efficacies. Also the main side-effects are described