Advances in understanding hypopituitarism

Abstract

The understanding of hypopituitarism has increased over the last three years. This review provides an overview of the most important recent findings. Most of the recent research in hypopituitarism has focused on genetics. New diagnostic techniques like next-generation sequencing have led to the description of different genetic mutations causative for congenital dysfunction of the pituitary gland while new molecular mechanisms underlying pituitary ontogenesis have also been described. Furthermore, hypopituitarism may occur because of an impairment of the distinctive vascularization of the pituitary gland, especially by disruption of the long vessel connection between the hypothalamus and the pituitary. Controversial findings have been published on post-traumatic hypopituitarism. Moreover, autoimmunity has been discussed in recent years as a possible reason for hypopituitarism. With the use of new drugs such as ipilimumab, hypopituitarism as a side effect of pharmaceuticals has come into focus. Besides new findings on the pathomechanism of hypopituitarism, there are new diagnostic tools in development, such as new growth hormone stimulants that are currently being tested in clinical trials. Moreover, cortisol measurement in scalp hair is a promising tool for monitoring cortisol levels over time.

VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1dw/dw) mice

“…Combined deficiencies of growth hormone, thyrotropin, and prolactin are typical in congenital hypopituitarism, a form of hypopituitarism in which mutation in PIT1 is a common genetic cause (Stieg et al, 2017; Takagi et al, 2017). The present study characterizes in the Snell dwarf ( Pit1 dw/dw ) mouse model, the impact of such combined deficiencies on skeletal muscle mass, function, and response to resistance‐type exercise training.…”

“…The Snell dwarf mouse, first described in 1929, is one such genetic model with a recessive mutation in Pit1 (Pou1f1) , an anterior pituitary transcriptional factor (Snell, 1929). PIT1 is among the most common genes mutated in genetic cases of patients with combined pituitary hormone deficiencies with more than 30 distinct PIT1 mutations identified to date (Stieg, Renner, Stalla, & Kopczak, 2017; Takagi et al, 2017). Such hypopituitarism results as a consequence of compromised anterior pituitary development, and clinical manifestation includes several various forms of muted development overall and short stature (Lee et al, 2011).…”

A clinical case of partial hypopituitarism

“…В зависимости от клинических проявлений выделяют изолированный ГП (при выпадении одной тропной функции), частичный, или парциальный (в случае нарушения двух тропных функций и более, но не всех), а также пангипопитуитаризм (при поражении всех тропных функций). Первичный ГП развивается вследствие отсутствия или разрушения секреторных клеток гипофиза, а вторичный -обусловлен дефицитом стимулирующих влияний на секрецию гипофизарных гормонов: нарушением сосудистых и/или нервных связей с мозгом на уровне ножки гипофиза; гипоталамуса или внегипоталамических областей центральной нервной системы [5,6].…”

“…Причинами развития недостаточности кровоснабжения гипофиза являются гормонально-активные и неактивные аденомы гипофиза; инфильтративные процессы (аутоиммунный лимфоцитарный гипофизит, гранулематоз); послеродовой некроз гипофиза или синдром Шихана, возникший при кровотечениях во время родов; последствия хирургических или лучевых вмешательств в области гипофиза; инфаркты гипофиза; метастазы в гипофиз или в ножку гипофиза; травмы, инфекции, гемохроматоз, сосудистые нарушения; редкие причины ГП (диабетическая ангиопатия и серповидно-клеточная анемия). При разрушении не менее 75% всей гипофизарной ткани развивается ГП, при котором недостаточно вырабатываются тропные гормоны гипофиза, развивается гипотиреоз и надпочечниковая недостаточность [6,7]. Генетические исследования больных пациентов и их семей дают представление о возможных механизмах аномального развития гипофиза, однако мутации встречаются редко [8].…”

Glucagon stimulation test: has its time come?

“…Hopefully, new technological improvements and assays developments will enable future diagnosis of SAI and GHD without stimulation tests. Analysis of cortisol in human scalp hair and quantitation of IGF-I by mass spectrometry has gained more attention in recent years and are just two examples of potential tools that may prove to be more reliable, robust and accurate than those currently in use [17][18][19]. Meanwhile, the time of GST has come as the most valuable alternative to ITT for diagnosing patients with SAI and GHD, mainly due its large availability and ability of assessing both cortisol and GH reserve simultaneously.…”