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GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11.

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretio

Factors influencing the outcome of microsurgical transsphenoidal surgery for pituitary adenomas: a study on 184 patients.

OBJECTIVE: Evaluation of factors influencing the outcome of microsurgical transsphenoidal surgery in patients harbouring pituitary adenomas as well as of the efficacy and safety of this procedure. DESIGN: A total of 184 consecutive patients with pituitary adenomas, undergoing microsurgical transsphenoidal resection of their lesions from March 2004 to June 2011, were prospectively studied. Extent of tumour resection and disease remission were defined according to recently established radiological and hormonal consensus criteria. RESULTS: The study included 97 nonfunctioning and 87 functioning

Measurement of human luteinizing hormone in plasma by radioimmunoassay.

The recent isolation of highly purified human pituitary luteinizing hormone (LH) has permitted the development of a sensitive and specific radioimmunoassay for this hormone in plasma. Results of this immunoassay system employing anti-LH serum agree closely with previous reports for the measurement of plasma LH in which immunoassays employing cross-reactive antisera to human chorionic gonadotropin were used. The immunoassay and bioassay of LH in several crude and partially purified pituitary and urinary extracts show acceptable agreement. The sensitivity of the LH immunoassay (0.2 mmug/ml) is a

Diseases associated with hidranitis suppurativa: part 2 of a series on hidradenitis.

Hidradenitis suppurativa (HS), a pathologic follicular disease, impacts patients' lives profoundly and usually occurs in isolation. The dise … h HS also. Single case reports of diseases associated with HS include systemic lupus erythematosus, acromegaly, Down syndrome, Bazex-Dupre´-Christol, and prurtis ani, but these might be coincidences. Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA Syndrome) and Pyoderma gangrenosum, Acne, and Suppurative Hidradenitis (PASH Syndrome) are pyodermic-ar …

Characteristics of clinical trials in rare vs. common diseases: A register-based Latvian study.

BackgroundConducting clinical studies in small populations may be very challenging; therefore quality of clinical evidence may differ between rare and non-rare disease therapies.ObjectiveThis register-based study aims to evaluate the characteristics of clinical trials in rare diseases conducted in Latvia and compare them with clinical trials in more common conditions.MethodsThe EU Clinical Trials Register (clinicaltrialsregister.eu) was used to identify interventional clinical trials related to rare diseases (n = 51) and to compose a control group of clinical trials in non-rare diseases (n = 1

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… Multidrug-resistant tuberculosis (MDR-TB) was the most studied condition, with 7 trials (13.7%), followed by chronic lymphocytic leukemia (CLL), with 4 trials (7.8%), and chronic myelogenous leukemia (Ph+ CML), acromegaly, and pseudomonas aeruginosa infection in cystic fibrosis, with 3 trials (5.9%) … | Phase II, open label | | GH levels | 8 | 10 | 24 | 24 Dopastatin (BIM-23A760) | Acromegaly | Phase II, open label | | GH and IGF-1 levels | 14 | 5 | 60 | 80 Dopastatin (BIM-23A760) | Carcinoid syndrome | Phase II, open label | | Symptom relief (diarrhea and/ or flushes) | 17 | 10 | 60 | 80 Tobramycin …

Diagnosis and treatment of pituitary adenomas.

Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specifi…

RET signalling provides tumorigenic mechanism and tissue specificity for AIP-related somatotrophinomas.

It is unclear how loss-of-function germline mutations in the widely-expressed co-chaperone AIP, result in young-onset growth hormone secreting pituitary tumours. The RET receptor, uniquely co-expressed in somatotrophs with PIT1, induces apoptosis when unliganded, while RET supports cell survival when it is bound to its ligand. We demonstrate that at the plasma membrane, AIP is required to form a complex with monomeric-intracellular-RET, caspase-3 and PKCδ resulting in PIT1/CDKN2A-ARF/p53-apoptosis pathway activation. AIP-deficiency blocks RET/caspase-3/PKCδ activation preventing PIT1 accumulat

Health technology assessment of drugs for rare diseases: insights, trends, and reasons for negative recommendations from the CADTH common drug review.

BackgroundA shift in biochemical research towards drugs for rare diseases has created new challenges for the pharmaceutical industry, government regulators, health technology assessment agencies, and public and private payers. In this article, we aim to comprehensively review, characterize, identify possible trends, and explore reasons for negative reimbursement recommendations in submissions made to the Common Drug Review (CDR) for drugs for rare diseases (DRD) at the Canadian Agency for Drugs and Technologies in Health (CADTH), a publicly funded pan-Canadian health technology assessment agen

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… Biologic/Growth hormone receptor antagonist Acromegaly 5.5 a Do not list 24/02/2006 Remodulin Treprostinil sodium Northern Theraputics Inc. Chemical/Vasodilating Agents Pulmonary arterial hypertension 3.3 a List with criteria/condition 20/07/2006 Sutent sunitinib Pfizer Canada Inc. … Biologic/Enzyme replacement therapy Glycogen storage disease type II 0.8 a List with clinical criteria and/or conditions 20/02/2007 Somatuline lanreotide acetate Ipsen Limited Chemical/Somatostatin Analog Acromegaly 5.5 a List in a similar manner to other drugs in class 22/06/2007 Thelin Sitaxsentan …

National guidelines for diagnosis and treatment of osteoporosis in Slovakia.

BACKGROUND: Osteoporosis is a chronic, systemic skeletal disease characterized by decreased bone mass and microarchitectural deterioration, leading to increased fracture risk. In Slovakia, its prevalence is estimated at 6%, with substantial health, social, and economic burdens. OBJECTIVE: The Slovak national guideline provides an overview for the diagnosis, prevention, and treatment of osteoporosis in Slovakia, reflecting recent scientific advances and recommendations from international bodies. METHODS: The guidelines were developed by a multidisciplinary expert panel and officially adopted

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… The most common causes of secondary osteoporosis include the following: - Osteoporosis with hormone deficiency: sex hormone and growth hormone deficiency - Osteoporosis due to an excess of hormones: hypercortisolism, hyperthyroidism, hyperprolactinemia, hyperparathyroidism, and acromegaly - Osteoporosis … TBS may also play a role in assessing fracture risk in some causes of secondary osteoporosis in which bone density is poorly correlated with this risk (e.g., type 2 DM, hyperparathyroidism, acromegaly, and glucocorticoid-induced osteoporosis). …

A year in pharmacology: new drugs approved by the US food and drug administration in 2025.

The US Food and Drug Administration approved 45 new drugs and 4 new cellular and gene therapy products in 2025, that is, a total of 49 new medical therapies. Oncology, hematology/immunotherapy, and cardiovascular/respiratory drugs remain most frequent. Among oncology drugs, there is a trend for targeting ever smaller subtypes of malignancies and/or rarer malignancies. Trends over the past 6 years include steady levels of first-in-indication (about 10%), first-in-class (about 38%), and next-in-class (about 51%) approvals. Along with a large share of approvals in orphan indications (> 50%), fast

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… A somatostatin receptor agonist, paltusotine , is approved to treat acromegaly in adults who have not achieved an adequate response to surgery or for whom surgery is not an option. … Transitioning patients with acromegaly from injectable somatostatin receptor ligands to once-daily oral paltusotine maintained biochemical control and was well tolerated. Hormone levels rise after paltusotine treatment withdrawal, supporting its effectiveness (Gadelha et al. 2023 ). …

Pituitary tumors: pathophysiology, clinical manifestations and management.

Pituitary tumors are frequently encountered intracranial neoplasms. They present with a variety of clinical manifestations that include symptoms and signs of excessive hormone secretion by the tumor, signs of hormone deficits by the normal pituitary gland and others related to expansion of the tumor mass and the resulting compression of surrounding structures such as the optic chiasm and cranial nerves. Advances in molecular biology, immunocytochemical staining and imaging, and the introduction of new treatment options have improved our understanding of the natural history of these adenomas an

Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases.

BackgroundPrevious evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas.MethodsMedicines for oncological, metabolic and infectious di

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… degludec a | Diabetes mellitus type 1 | HbA1c | DDG Ivacaftor | Cystic fibrosis | FEV1% | - Ivacaftor a | Cystic fibrosis | FEV1% | - Linagliptin b | Diabetes mellitus type 2 | HbA1c | BVND, DDG, Diabetes Research Group HZM Pasireotide | Pituitary gland dysfunction | mUFC ≤ ULN | - Pasireotide a | Acromegaly … For pasireotid (acromegaly) the PEP was biochemical control (defined as a combination of reduction of the mean growth hormone [GH] level below 2.5 μg/l and normalisation of the age- and sex-adjusted insulin-like growth factor 1 [IGF-1] level after 24 weeks). …

Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment.

Cancer incidence appears to be increased in both type 1 and type 2 diabetes mellitus (DM). DM represents a risk factor for cancer, particularly hepatocellular, hepatobiliary, pancreas, breast, ovarian, endometrial, and gastrointestinal cancers. In addition, there is evidence showing that DM is associated with increased cancer mortality. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in patients with DM. Although the mechanistic process that may link diabetes to cancer is not completely understood yet, biological mechanisms link

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… Furthermore, patients affected by acromegaly, a disorder characterized by excess of growth hormone and IGF-1, have been shown to have increased risks of several types of cancer [ 39 ]. … Acromegaly is associated with increased cancer risk: a survey in Italy. Endocr Relat Cancer. 2017;24:495–504. doi: 10.1530/ERC-16-0553. 40. Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, Martin-Hirsch P, Tsilidis KK. …