<abstract xmlns="http://www.w3.org/1999/xhtml">

Inherited metabolic disorders (IMDs ) are a rare and diverse group of metabolic conditions mainly caused by enzyme deficiencies, and in some of these, hormonal dysfunction is a relatively common complication. It may present in childhood and subsequently hormonal replacement is required throughout their life. Endocrinopathies can be a presenting symptom of an IMD in adulthood, which should be suspected when associated with multiorgan involvement (neurological, musculoskeletal or liver, etc.). A single IMD can affect any gland with hypogonadism, adrenal insufficiency, diabetes mellitus and thyroid dysfunction being the most common. In some cases, however, it is diagnosed later in their adult life as a secondary complication of previous therapies such as chemotherapy used during Haematopoietic Stem Cell Transplantation (HSCT) in childhood.
The mechanisms of endocrine dysfunction in this group of conditions are not well understood. Regardless, patients require ongoing clinical support from the endocrine, metabolic, bone metabolism and fertility specialists throughout their life.
Hormonal profiling should be part of the routine blood test panel to diagnose asymptomatic endocrine disorders with delayed manifestations. It is also worth considering screening for common hormonal dysfunction when patients exhibit atypical non-IMD related symptoms. In some adult-onset cases presenting with multiple endocrinopathies, the diagnosis of an IMD should be suspected.
Given that new therapies are in development (e.g. gene therapies, stem cell therapies, pharmacological chaperone and substrate reduction therapies), clinicians should be aware of their potential long-term effect on the endocrine system.
</abstract>

Inherited metabolic disorders (IMDs ) are a rare and diverse group of metabolic conditions mainly caused by enzyme deficiencies, and in some of these, hormonal dysfunction is a relatively common complication. It may present in childhood and subsequently hormonal replacement is required throughout their life. Endocrinopathies can be a presenting symptom of an IMD in adulthood, which should be suspected when associated with multiorgan involvement (neurological, musculoskeletal or liver, etc.). A single IMD can affect any gland with hypogonadism, adrenal insufficiency, diabetes mellitus and thyroid dysfunction being the most common. In some cases, however, it is diagnosed later in their adult life as a secondary complication of previous therapies such as chemotherapy used during Haematopoietic Stem Cell Transplantation (HSCT) in childhood.
The mechanisms of endocrine dysfunction in this group of conditions are not well understood. Regardless, patients require ongoing clinical support from the endocrine, metabolic, bone metabolism and fertility specialists throughout their life.
Hormonal profiling should be part of the routine blood test panel to diagnose asymptomatic endocrine disorders with delayed manifestations. It is also worth considering screening for common hormonal dysfunction when patients exhibit atypical non-IMD related symptoms. In some adult-onset cases presenting with multiple endocrinopathies, the diagnosis of an IMD should be suspected.
Given that new therapies are in development (e.g. gene therapies, stem cell therapies, pharmacological chaperone and substrate reduction therapies), clinicians should be aware of their potential long-term effect on the endocrine system.

Hormonal dysfunction in adult patients affected with inherited metabolic disorders

Journal of Mother and Child

This work is licensed under the Creative Commons Attribution 4.0 International License.

Inherited metabolic disorders (IMDs ) are a rare and diverse group of metabolic conditions mainly caused by enzyme deficiencies, and in some of these, hormonal...

Endocrine gland	Endocrine dysfunction	Specific IMD example	Blood tests to screen for the endocrine
Pituitary	Hypopituitarism/Short stature	LSDs: MPS, sialidosis, gangliosidosis, mucolipidosis Others: haemochromatosis, acaeruloplasminaemia, Wilson’s disease, mitochondrial diseases, cystinosis, post-HSCT	TSH, free T4 and free T3, serum cortisol, LH, FSH, male testosterone/estradiol, SHBG, prolactin, IGF1, growth hormone
Pituitary	Hyperprolactinaemia	GTP cyclohydrolase deficiency, CDGs, GSD Ia	PRL
Thyroid	Hyperthyroidism	Fabry disease (prior to ERT), post-HSCT	TSH, free T4, free T3
	Hypothyroidism	Mitochondrial diseases, cystinosis, Fabry disease, GSD Ib, CGD, hyperoxaluria type I, neutral lipid storage disease	TSH, free T4, free T3, TBG
	Transient thyroiditis	post-HSCT	TSH, free T4, free T3, anti TPO antibodies
Parathyroid	Hypoparathyroidism	LCHAD, MCADD mitochondrial diseases (MELAS) haemochromatosis	Serum calcium, parathyroid hormone, alkaline phosphatase
Ovaries	Hypogonadism	Classical galactosaemia, SLO, CDG, mitochondrial diseases, post-HSCT	LH, FSH, serum estradiol, antimullerian hormone
Ovaries	PCOS	GSD Ia	LH, FSH, serum estradiol, prolactin
Testicles	Hypogonadism	Haemochromatosis, mitochondrial diseases, cystinosis, X-linked ALD, post-HSCT	Serum testosterone, SHBG, LH, FSH, inhibin B
Adrenal gland	Adrenal insufficiency	X-linked ALD, Lesch-Nyhan syndrome, peroxisomal disorders, Fabry disease, mitochondrial diseases, post-HSCT	Serum cortisol at 9am, short synacthen test, fasting glucose
Pancreas	Diabetes/insulin resistance	Mitochondrial diseases, haemochromatosis, acaeruloplasminaemia, Wilson’s disease, cystinosis, organic acidurias, respiratory chain disorders, GSD I, III and V, Alström syndrome, CDGs	Random glucose, HbA1c, lipid profile, urate

Hormonal dysfunction in adult patients affected with inherited metabolic disorders

Article Category: Review paper

Published Online: Nov 10, 2020

Page range: 21 - 31

DOI: https://doi.org/10.34763/jmotherandchild.20202402si.2018.000005

Keywords
inherited metabolic disorder, endocrine dysfunction, hormones, hypogonadism, thyroid, diabetes mellitus, adrenal failure

© 2020 Karolina M. Stepien, published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Endocrine dysfunction in inherited metabolic disorders

Hormonal dysfunction in adult patients affected with inherited metabolic disorders

Article Category: Review paper

Published Online: Nov 10, 2020

Page range: 21 - 31

DOI: https://doi.org/10.34763/jmotherandchild.20202402si.2018.000005

Keywordsinherited metabolic disorder, endocrine dysfunction, hormones, hypogonadism, thyroid, diabetes mellitus, adrenal failure

© 2020 Karolina M. Stepien, published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Endocrine dysfunction in inherited metabolic disorders

Keywords
inherited metabolic disorder, endocrine dysfunction, hormones, hypogonadism, thyroid, diabetes mellitus, adrenal failure