Unusual and lesser-known rare causes of adult growth hormone deficiency

Available online 28 August 2023, 101820

Best Practice & Research Clinical Endocrinology & Metabolism

Author links open overlay panel, ABSTRACT

Growth hormone is among the most common hormones to be deficient in pituitary insult. It can occur either in isolation or combined with other hormone deficiencies. Growth hormone deficiency in adults (AGHD) can be due to causes acquired in adulthood or have a childhood-onset etiology, but the former is about three times more common. Usual causes of AGHD include mass effects due to a pituitary tumour, and/or its treatment (surgery, medical therapy, or radiotherapy), or radiotherapy to the head and neck region for non-pituitary lesions. The unusual or lesser-known causes of AGHD, are usually due to non-tumoral etiology and range from vascular and infective to inflammatory and miscellaneous causes. These not only expand the spectrum of AGHD but may also contribute to increased morbidity, adverse metabolic consequences, and mortality in the primary condition, if unrecognised. The review features these lesser-known and rare causes of AGHD and highlights their clinical and diagnostic implications.

Section snippetsCase vignette

A 33-year-old female presented to the adult endocrinology clinic with polyuria-polydipsia and a preference for cold liquids at 28 years of age, 18 months following the delivery of her second child (Fig. 1). She had noticed an onset of symptoms 1 year following delivery. She also complained of an intermittent dull headache, diarrhoea, and weight loss (nearly 10 kg over 4 months). Her past medical history was otherwise unremarkable. Menstrual cycles were normal. On examination, her stature was

Background

Growth hormone is among the most common hormones to be affected in the event of pituitary insult. It is affected in nearly 50 to 72% of cohorts with hypopituitarism [1], [2], [3]. Growth hormone is one of the earliest to be involved in various pituitary insults, hence it may be an isolated deficiency or occur concurrently with other hormone deficiencies. Though AGHD may be due to childhood-onset or acquired adult-onset causes, the latter is the predominant contributor to AGHD (almost 77% in the

Clinical perspective

Growth hormone deficiency resulting from usual causes such as a pituitary adenoma and/or its management is more likely to be recognised, diagnosed, and managed earlier than GHD due to an unusual cause. The symptoms of GHD due to an unusual cause are non-specific, and the onset, progression variable, which compounds the complexity and challenges. Notwithstanding, diagnosis of GHD due to less common causes should be individualised, based on signs/symptoms and associated features of the underlying

SUMMARY

GHD in adults is most commonly caused by a pituitary adenoma and/or its therapy. Unusual causes of GHD are mostly non-tumoral and comprise a heterogeneous spectrum, including infective, vascular, traumatic, inflammatory, and other rare causes. The bottom line for GHD in all these settings is that it may be present in acute settings or on follow-up, often underestimated due to less focus on its diagnosis in acute settings (as it is not a life-saving hormone) as well as lack of robust definitive

Uncited references

[49], [78]

Funding

There was no funding for the manuscript.

Conflict of interest

The authors have no conflicts of interest to declare.

Acknowledgment

We wish to thank Prof. Uma Nahar Saikia, Department of Histopathology, PGIMER Chandigarh for providing the histopathological images of the case of GHD due to celiac disease.

We also wish to thank Mr. Brijlal Badhan, Senior Technical Officer, Department of Clinical Photography, PGIMER Chandigarh.

REFERENCES (80)G. Brabant et al.Etiology, baseline characteristics, and biochemical diagnosis of GH deficiency in the adult: are there regional variations?

European Journal of Endocrinology

(2009 Nov 1)

I.C. Van Nieuwpoort et al.Dutch National Registry of GH Treatment in Adults: patient characteristics and diagnostic test procedures

European journal of endocrinology

(2011 Apr)

U. Feldt-Rasmussen et al.Adult Growth Hormone Deficiency- Clinical Management. [Updated 2022 May 23]S.M. Webb et al.HypoCCS International Advisory Board. Changing patterns of the adult growth hormone deficiency diagnosis documented in a decade-long global surveillance database

The Journal of Clinical Endocrinology & Metabolism

(2009 Feb 1)

S. MelmedIdiopathic adult growth hormone deficiency

The Journal of Clinical Endocrinology & Metabolism

(2013 Jun 1)

S. Pekic et al.Hypopituitarism Following Cranial Radiotherapy. [Updated 2021 Aug 9].N.M. Appelman-Dijkstra et al.Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis

The Journal of Clinical Endocrinology & Metabolism

(2011 Aug 1)

L. Das et al.Approach to the patient: A case with an unusual cause of hypopituitarism

The Journal of Clinical Endocrinology & Metabolism

(2023 Jun)

K.S. Lam et al.Hypopituitarism after tuberculous meningitis in childhood

Annals of internal medicine

(1993 May 1)

Z. Karaca et al.Sheehan syndrome

Nature Reviews Disease Primers

(2016 Dec 22)

F. KeleştimurSheehan's syndrome

Pituitary.

(2003 Dec)

H. Diri et al.Extensive investigation of 114 patients with Sheehan's syndrome: a continuing disorder

European journal of endocrinology

(2014 Sep)

F. Kelestimur et al.Sheehan’s syndrome: baseline characteristics and effect of 2 years of growth hormone replacement therapy in 91 patients in KIMS–Pfizer International Metabolic Database

European Journal of Endocrinology

(2005 Apr)

L. Das et al.Long-term hepatic and cardiac health in patients diagnosed with Sheehan’s syndrome

Pituitary.

(2022 Dec)

H. Singh et al.Prevalence of coronary calcium deposits in Sheehan’s syndrome patients on long term replacement treatment

Pituitary.

(2022 Feb 1)

B.N. Naik et al.Pituitary dysfunction in survivors of Russell's viper snake bite envenomation: A prospective study

Neurology India

(2018 Sep 1)

C. Shivaprasad et al.Delayed hypopituitarism following Russell’s viper envenomation: a case series and literature review

Pituitary.

(2019 Feb 15)

C.N. Antonypillai et al.Hypopituitarism following envenoming by Russell’s vipers (Daboia siamensis and D. russelii) resembling Sheehan’s syndrome: first case report from Sri Lanka, a review of the literature and recommendations for endocrine management

QJM: An International Journal of Medicine

(2011 Feb 1)

V. Golay et al.Hypopituitarism in patients with vasculotoxic snake bite envenomation related acute kidney injury: a prospective study on the prevalence and outcomes of this complication

Pituitary.

(2014 Apr)

C.C. van Bunderen et al.Efficacy and safety of growth hormone treatment in adults with growth hormone deficiency: a systematic review of studies on morbidity

Clinical endocrinology

(2014 Jul)

I. Karamouzis et al.Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS)

Endocrine.

(2016 Jun)

M. Bondanelli et al.Predictors of pituitary dysfunction in patients surviving ischemic stroke

The Journal of Clinical Endocrinology & Metabolism

(2010 Oct 1)

H.J. Schneider et al.Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review

Jama.

(2007 Sep 26)

G. Vieira Jr et al.Long-term follow-up of anterior pituitary deficiency after aneurysmal subarachnoid hemorrhage: prospective cohort

Journal of Stroke and Cerebrovascular Diseases

(2016 Oct 1)

A. Can et al.Pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Neurosurgery.

(2016 Aug 1)

C.J. Gardner et al.Low prevalence of hypopituitarism after subarachnoid haemorrhage using confirmatory testing and with BMI-specific GH cut-off levels

European Journal of Endocrinology

(2013 Apr)

M. Bondanelli et al.Prevalence of hypopituitarism in patients with cerebrovascular diseases

Journal of Endocrinological Investigation

(2008 Sep 1)

L.A. Kreber et al.Prevalence of growth hormone deficiency in middle-age adults recovering from stroke

Brain Injury

(2020 Jan 28)

V. Gasco et al.Traumatic brain injury as frequent cause of hypopituitarism and growth hormone deficiency: epidemiology, diagnosis, and treatment

Frontiers in endocrinology

(2021 Mar 15)

M. Kałas et al.Post-Traumatic Hypopituitarism: A Neglected Consequence of Traumatic Brain Injury