Aspects of diagnosis and treatment of hypopituitarism in adult life
Abstract
Management of adult patients with hypopituitarism can improve with better char¬ac¬terisation of idiopathic pituitary insufficiency (IPI) and clearer diagnosis of central hy¬pothy¬roidism (CH). Moreover, optimised treatment strategies for glucocorticoid (GC) re¬placement therapy and of long-term growth hormone (GH) in GH deficiency (GHD) are needed.
This thesis contains four studies addressing these issues. By evaluating patients with IPI, mutations generating hypopituitarism were identified in an unselected adult IPI population. A new allel constellation in a compound PROP1 mutation was re¬vealed in two siblings, with a phenotype of very late onset ACTH-insufficiency. Those cases were only detected in patients with documented childhood onset disease. A pilot study investigated the response of the thyroid gland after stimulation with 0.9 mg re¬combinant human thyreotropin (rhTSH) in patients with newly diagnosed CH and healthy controls. The untreated CH patients had lower free thyroxine response than controls. A database study containing 2424 hypopituitary patients, di¬vided into ACTH-insufficient and ACTH-sufficient (AS) patients, demonstrated a clear GC dose-re¬sponse relation with metabolic outcome. Patients with hydrocortisone equivalent doses of <20 mg/day had a similar metabolic profile as AS patients. In a large study on GHD patients on long-term GH treatment quality of life (QoL), body composition, and metabolic outcome were evaluated during 4-month-GH-dis¬continuation in a dou¬ble blind, placebo controlled design. QoL deteriorated, body com¬position moved towards a GHD state and metabolic parameters were impaired during placebo treatment.
These studies infer that genetic hypopituitarism should be searched for in IPI cases, especially in childhood onset disease and where there is a family history. The diag¬nosis of CH can be improved by an rhTSH test. In many cases, doses of GC can be reduced in ACTH-insufficient patients in order to improve their metabolic outcome and continuous long-term GH replacement is needed to maintain beneficial effects on QoL, body composition, and metabolism.
Parts of work
I. Detection of genetic hypopituitarism in an adult population of idiopathic pitui¬tary insufficiency patients with growth hormone deficiency. Filipsson H, Savaneau A, Barbosa E L J, Barlier A, Enjalber A, Glad C, Palming J, Johannsson G, Thierry B. Manuscript II. Exploring the use of recombinant human thyrotropin in the diagnosis of central hypothyroidism. Filipsson H, Nyström E, Johannsson G. European Journal of Endocrinology 2008 Aug;159(2):153-60 ::pmid::18511470 III. The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients. Filipsson H, Monson JP, Koltowska-Häggström M, Mattsson A, Johannsson G. Journal of Clinical Endocrinology and Metabolism 2006 Oct;91(10):3954-61 ::pmid::16895963 IV. Discontinuation of long-term GH replacement therapy – a randomised, pla¬cebo controlled trial in adult GH deficiency. Filipsson H, Barbosa E L J, Nilsson AG, Norrman L, Ragnarsson O, Johannsson G. Manuscript
Degree
Doctor of Philosophy (Medicine)
University
University of Gothenburg. Sahlgrenska Academy
Institution
Institute of Medicine. Department of Internal Medicine
Disputation
Fredagen den 20 mars 2009, kl 9.00, i sal Förmaket, Blå stråket 5, Sahlgrenska Universitetssjukhuset, Göteborg
Date of defence
2009-03-20
helena.filipsson@telia.com
Date
2009-02-27Author
Filipsson, Helena
Keywords
hypopituitarism
pituitary
diagnosis
treatment
GHD
central hypothyroidism
genetic
idiopathic
ACTH insufficiency
discontinuation
Publication type
Doctoral thesis
ISBN
978-91-628-7694-4
Language
eng