CLINICAL: PATHOPHYSIOLOGY

The endocrine system and

associated disorders
Emily Ashwell

the secretions (hormones) to the desired location, for example

ABSTRACT sweat from glands in the skin (Khan et al, 2022). In contrast,
The endocrine system and the hormones it produces control a range of endocrine glands release their secretions into the bloodstream,
processes in the body, as well as helping to maintain homeostasis. When as part of their primary function. Therefore, endocrine glands
this complex system is disrupted, including by changes associated with have a rich blood supply to ensure efficient transport of their
ageing, disease may result. This article provides an overview of the endocrine hormones around the body and enable them to continuously
systems, key glands and hormones, and some of the problems that can monitor blood for changes that initiate hormone secretion
arise from disruption to the system. A case study is provided to illustrate (Fox et al, 2015) (Figure 1).
one possible presentation of endocrine disruption, in the form of diabetes- The hypothalamus is a part of the brain that releases several
associated complications. hormones, which affects other endocrine glands’ hormone
Key words: Endocrine system ■ Medical conditions ■ Endocrine conditions production, acting as the endocrine control centre and
■ Endocrine medicine ■ Hormones
linking the nervous system with the endocrine system (Fox
et al, 2015). This is connected to the pituitary gland, which

T
produces hormones controlling growth, metabolism, and sexual
he endocrine system comprises several distinct glands development.The pineal gland is also located in the brain and
and tissues, which are made up of specialised cells that produces melatonin, which affects wakefulness (Tan et al, 2018).
synthesise, store, and secrete hormones. Hormones are Outside of the brain there is the thyroid gland, which sets
chemical messengers that can act on nearby cells via the body’s metabolic rate, the parathyroid glands, which control
interstitial fluid (paracrine effect), on the cell of origin the absorption and excretion of calcium and phosphate, and
(autocrine effect), at a distant site (endocrine or exocrine effects), the thymus gland, which releases thymosin, stimulating the
or as neurotransmitters (Knight, 2021). Neurotransmitters across production of immune T cells (Fox et al, 2015). The adrenal
synapses contribute to the rapid actions of the nervous system. In glands, located on top of each kidney, control blood pressure, fluid
contrast, endocrine effects tend to be slow to develop and result and electrolyte balance, and the body’s response to physiological
in prolonged responses potentially lasting weeks, as hormones and psychological stress (Andrade et al, 2021). The endocrine
travel in the bloodstream from an endocrine gland to another glands of the pancreas secrete insulin and glucagon, which
organ. Hormones control a wide range of physiological processes, together regulate blood glucose concentration. Reproductive
including growth, metabolism, sleep, immune system response, glands (testes in males and ovaries in females) release sex
‘fight or flight’, reproduction, mood, and behaviour (Kumar and hormones that enable reproduction and sexual maturation
Clark, 2017).They also assist in maintaining homeostasis (a state (Figure 2). In addition, the intestine and adipose tissue also
of physiological equilibrium) by regulating the body’s internal secrete hormones as part of their primary function, although
environment in response to changes in the external environment. these are not major endocrine glands. Other organs, such as
The human body produces more than 100 hormones to carry the liver, kidney, heart, and skin all have secondary endocrine
out these processes, and research is continuing to further our functions (Fox et al, 2015).
understanding of their functions and interactions as well as
identifying more hormones (Knight, 2021). Hormone signalling pathways
Hormones are grouped into three chemical classes: peptides,
Endocrine and exocrine glands amines, and lipids (mainly steroids) and are synthesised by
All glandular tissues produce secretions. Exocrine glands are endocrine glands cells before being stored in preparation for
arranged so they secrete theirs via a central duct, which directs rapid secretion as required (Fox et al, 2015). On release they
are transported through the body in the blood, where they
© 2022 MA Healthcare Ltd

then employ their desired physiological effects by binding

Emily Ashwell, Community Caseload Manager Nurse, to specific receptors on the outer membrane or within their
Buckinghamshire Healthcare NHS Trust target cells. Intracellular binding directly affects the cell’s gene
Accepted for publication: March 2022 expression, whereas extracellular binding changes the cell’s
metabolism through cascade reactions. Many medications

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 CLINICAL: PATHOPHYSIOLOGY

have been created to target these receptor sites by imitating a

hormone’s action (for example, people with hypothyroidism
can be given levothyroxine to mimic the thyroxine they are
lacking), or by acting as a competitive antagonist, blocking
target receptors to prevent the hormone from binding and
employing its effect (for example, beta blockers can be used
to treat the adrenaline-related symptoms of hyperthyroidism)
(Knight, 2021). Once used, hormones are then released from
the target cells either unchanged or inactivated and transported
to the liver or kidneys to be broken down and excreted as bile
or urine, respectively.

designua/ADOBESTOCK
Hormone production is controlled with feedback loops.
Most often these involve negative feedback mechanisms,
where the effects of a hormone inhibit its release to maintain
homeostasis, such as the mechanisms involved in blood glucose
regulation (Figure 3). Hypoglycaemia and hyperglycaemia in
diabetes mellitus demonstrate deviation from a normal range
(in this case blood sugar), which can can be symptomatic and
contribute to more severe pathology. In positive feedback
mechanisms a hormone’s effects stimulate its secretion, for Figure 1. Endocrine and exocrine glands
example, in childbirth oxytocin is released, stimulating uterine
contractions and pushing the baby towards the cervix, which
stimulates the release of more oxytocin (Walter et al, 2021).

Aetiology of endocrine disorders

Disturbance at any point in these complex processes or
development of these glands can result in disease. Endocrine
disorders largely result from too much or too little hormone
secretion.This hormonal imbalance may be due to a problem
with the endocrine feedback system, genetic disorder,
infection, injury or disease of the endocrine gland, or the

LuckySoul/ADOBESTOCK
growth of nodules or tumours in the glands (Kumar and
Clark, 2017). For example, in Cushing’s disease the negative
feedback loop is disturbed so pituitary hormone ACTH
production may become excessive as it is not inhibited by
excessive cortisol, resulting in symptoms such as central
obesity and high blood pressure. Ageing also lessens the
endocrine system’s functioning, as the secretion of several
hormones is reduced, along with target cells sensitivity to the Figure 2. The major endocrine glands and their position in the body
hormones produced. Examples include falling oestrogen levels
triggering menopause, decreasing growth hormone causing Adipocytes Consume Glucose
Glucose
loss of muscle mass, declining melatonin levels disturbing
sleep, and insulin sensitivity reducing, which increases the risk High Glucose Restore to Normal Gluose
Low Glucose Level
of diabetes—although these changes fluctuate significantly
between individuals (van den Beld et al, 2018). Children are
also at risk of endocrine disorders, most commonly thyroidal
dysfunctions, diabetes, cryptorchidism, precocious puberty, and Insulin 1

pancreatic and thyroid cancers (World Health Organization 1 1

1
(WHO), 2012).
Diagnosis of endocrine disorders is based on signs and Pancrease

symptoms, physical examination, medical history, imaging tests

uday/ADOBESTOCK

2
2
to detect tumours, and blood and urine analysis to determine
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Glucagon
the levels of hormone within them. Once diagnosed treatment 2 2
can be targeted to the specific disorder and individual,
managing their symptoms and maintaining homeostasis with Liver Releases Glucose

medications, surgery, chemotherapy, or radiation therapy as

required (Knight, 2021). Figure 3. The negative feedback mechanism for maintaining blood glucose

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CLINICAL: PATHOPHYSIOLOGY

Endocrine disorders in high-income countries, but iodine deficiency remains a major

Although not exhaustive, Table 1 gives some examples of hormones cause in many parts of the world (Knight et al, 2021). Iodine is
and disorders for key glands. Table 2 gives an elaboration of the also vital during pregnancy as thyroid hormones are essential
cause and signs and symptoms for a disorder for each gland. for neurological development and the foetus relies entirely on
maternal thyroid hormones until about 14 weeks’ gestation when
Hypothyroidism it begins to produce its own (Taylor et al, 2018). Autoimmune
Thyroid diseases are among the most common of the endocrine thyroiditis with inflammation of the thyroid (goitre) is called
disorders and can affect people of all ages. The most common Hashimoto’s thyroiditis and occurs when the follicular
of these disorders is hypothyroidism, where the thyroid gland components of the thyroid gland are progressively destroyed by
is underactive, resulting in a deficiency of T3 and T4 in the the patient’s own immune system, resulting in reduced secretion
bloodstream (Knight et al, 2021). Hypothyroidism caused by of T3 and T4, and a reduced metabolic rate. Most individuals
diseases of the thyroid gland, such as infection, inflammation, with mild hypothyroidism have non-specific symptoms including
or deficiency, is known as primary hypothyroidism and is tiredness, lethargy, weight gain and depression, all of which
more likely to affect women. When hypothyroidism results are common in the general population. Therefore, diagnosis is
from pituitary or hypothalamic disorders, including benign or confirmed with biochemical tests (Taylor et al, 2018).
malignant growths or following head trauma, it is known as Once diagnosed treatment for hypothyroidism usually
secondary hypothyroidism (Taylor et al, 2018). Autoimmune involves taking the drug levothyroxine, a synthetic form of
thyroiditis is the most common cause of primary hypothyroidism T4. The dose of levothyroxine is calculated based on body
weight, except in the case of people with ischaemic heart
Table 1. Glands and their disorders disease who are given a lower dose as it can precipitate severe
Gland Hormones produced Disorders
angina (Kumar and Clark, 2017).

Hypothalamus ■ Thyrotropin-releasing hormone (TRH) ■ Central diabetes Hyperthyroidism

■ Corticotrophin-release hormone insipidus
Hyperthyroidism is caused when an overactive thyroid gland
(CRH) ■ Depression
■ Growth hormone-releasing hormone ■ Anxiety excretes excessive amounts of hormones. This affects around
(GHRH) 2% of women and 0.2% of men, with the incidence increasing
■ Arginine vasopressin (AVP) with age in both sexes (National Institute for Health and
Pituitary gland ■ Thyroid-stimulating hormone (TSH) ■ Acromegaly
Care Excellence (NICE), 2019). Graves’ disease is the most
(anterior) ■ Adrenocorticotropic hormone (ACTH) ■ Dwarfism common form of hyperthyroidism. It is an autoimmune
■ Follicle-stimulating hormone (FSH) ■ Multiple endocrine disorder, characterised by the signs and symptoms shown in
■ Luteinising hormone (LH) neoplasia type 1 (MEN 1) Table 2, where antibodies are produced that bind to the same
■ Growth hormone (GH) ■ Pituitary tumours receptors as TSH and subsequently increase metabolic rate,
■ Prolactin
raising the body’s core temperature, which leads to increased
(posterior) ■ Oxytocin sweating and weight loss (Knight et al, 2021). Graves’ disease
■ Antidiuretic hormone (ADH) can also cause a build-up of inflamed, fibrous, fatty tissue
Thyroid ■ Triiodothyronine (T3) ■ Grave’s disease behind the eyes, causing them to bulge.
■ Thyroxine (T4) ■ Hyperthyroidism Risk factors for Graves’ disease include smoking and being
■ Calcitonin ■ Thyroiditis female (Wémeau et al, 2021). Hyperthyroidism can be treated
■ Nodules and cancers using anti-thyroid drugs or radioactive iodine (radioiodine)
■ Hypothyroidism
therapy that works by damaging and killing some of the follicular
■ MEN 2A and 2B
cells that secrete hormones, although this is not suitable for
Parathyroid ■ Parathyroid hormone (PTH) ■ Hypoparathyroidism pregnant or breastfeeding women (Subekti and Pramono, 2018)
■ MEN 1, 2A and 2B

Pancreas ■ Glucagon ■ Type 1 diabetes mellitus Case study

■ Insulin ■ Type 2 diabetes mellitus Presentation
■ Gestational diabetes Ms Singh is 56 years old and attends her GP after a week of severe
■ MEN 1
itching (pruritus) and noticing thick white vaginal discharge.
Adrenal ■ Androgens ■ Addison’s disease
■ Glucocorticoids ■ Cushing’s syndrome Initial interpretation
■ Androgens ■ MEN 2A and 2B
Sexually transmitted diseases should be considered as a potential
■ Adrenaline
■ Noradrenaline cause of vaginal discharge. However, in a woman over 50 years
old, thrush (Candida albicans) is the most common cause (Al
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Ovary ■ Oestrogens ■ Polycystic ovarian Halteet et al, 2020).

■ Progesterone syndrome
■ Turner syndrome
History
Testes ■ Testosterone ■ Kallmann’s syndrome Ms Singh had two previous episodes of thrush in the past
■ Haemochromatosis
few months, which she self-medicated with over-the-counter

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 CLINICAL: PATHOPHYSIOLOGY

Table 2. Examples of signs and symptoms of endocrine disorders

Gland Disorder Cause Signs and symptoms

Hypothalamus Central diabetes insipidus Deficiency of AVP, an antidiuretic hormone that acts ■ Polyuria
on receptors in kidney to promote water reabsorption ■ Polydipsia
(Arima, 2016)

Pituitary gland Acromegaly Excessive GH production by the anterior pituitary ■ Broadening of hands, feet,
gland. Most commonly due to pituitary adenoma and facial features
(Caron et al, 2019) ■ Headaches
■ Visual field defects

Thyroid Grave’s disease Autoimmune disease that causes the thyroid to grow ■ Goitre
and produce an excess of thyroid hormone (Subekti ■ Bulging eyes
and Pramono, 2018) ■ Skin thickening
■ Difficulty sleeping
■ Fatigue
■ Heat intolerance
■ Weight loss

Parathyroid Hypoparathyroidism Inadequate parathyroid hormone production, most ■ Tingling in the hands and
commonly due to damage or removal of parathyroid around the mouth
glands during surgery (Norman, 2018) ■ Muscle cramps

Pancreas Type 1 diabetes mellitus Autoimmune response damages pancreas cells so ■ Polydipsia
they are unable to produce sufficient insulin (Fox et ■ Polyuria
al, 2015) ■ Fatigue
■ Weight loss
■ Vision changes

Adrenal Addison’s disease The adrenal glands do not produce enough cortisol ■ Fatigue
(Andrade et al, 2021) ■ Abdominal pain
■ Nausea
■ Weight loss
■ Hypotension

Ovary Polycystic ovarian syndrome The exact cause of is uncertain, although some ■ Irregular menstrual cycle
individuals make extra androgens such as ■ Weight gain
testosterone (Escobar-Morreale, 2018) ■ Hirsutism
■ Thinning hair
■ Infertility

Testes Kallmann’s syndrome Genetic condition resulting androgen deficiency (Liu ■ Decreased libido
and Zhi, 2021) ■ Gynaecomastia
■ Hearing loss

antifungal pessaries from the pharmacy. These temporarily (glycosuria). A random venous blood glucose reading of
improved her symptoms, which then reoccurred a few weeks 12.8 mmol/litre is above normal range, and later her blood test
later. She is finding the itching bothersome and was wondering if results show her haemoglobin A1c (HbA1c), a marker of long-
anything else can be prescribed to clear up the infection for good. term glucose levels, is also high at 68 mmol/mmol. Table 3 shows
Her husband has no symptoms, and she has had no new the WHO reference levels for these tests in diabetes diagnosis.
sexual contacts in the last 30 years. In the past year she has
been feeling increasingly tired and has put on 12 kg. Her older Table 3. World Health Organization criteria for diabetes mellitus diagnosis
brother was diagnosed with diabetes mellitus and recently died
Measurement Normal result Result in diabetes
following a stroke aged 64 years and her mother has several
lower leg ulcers. Random venous plasma glucose Variable ≥ 11.1
concentration (mmol/L)
Physical examination Fasting plasma glucose concentration ≤6 ≥7
Ms Singh is obese with a body mass index (BMI) of 36.4 kg/m2. (mmol/L)
Her blood pressure is raised at 148/94 mmHg. A sample of her
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Plasma glucose concentration 2 hours ≤ 7.7 ≥ 11.1

vaginal discharge, which is thick, white, and cottage-cheese like, after 75 g anhydrous glucose in an oral
has been sent for analysis. glucose tolerance test (mmol/L)

Haemoglobin A1c (mmol/mol) ≤ 41 ≥ 48

Further investigations
Urinalysis identifies the presence of glucose in her urine Source: WHO, 2011

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CLINICAL: PATHOPHYSIOLOGY

the physician’s and the patient’s perspectives in the ACRO-POLIS study.

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Fox T, Brooke A,Vaidya B. Eureka Endocrinology. 1st edn. London: JP Medical
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Goff LM. Ethnicity and type 2 diabetes in the UK. Diabet Med. 2019; 36(8): 927-
produce their desired effect on target cells 938. https://doi.org/10.1111/dme.13895
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Edinburgh: Elsevier; 2017
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021-00638-8
Interpretation of findings National Institute for Health and Care Excellence.Thyroid disease: assessment
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obesity and ethnicity are also predisposing factors for type 2 National Institute for Health and Care Excellence.Type 2 diabetes in adults:
diabetes mellitus (Goff, 2019). These factors alongside her test management. NICE Guidance NG28. 2022 (updated version of guidance first
published 2015). https://www.nice.org.uk/guidance/ng28 (accessed 14 March
results lead to Ms Singh being diagnosed with type 2 diabetes. 2022)
Her high glucose levels in the urine and blood allows yeasts to Norman J. Hypoparathyroidism: too little parathyroid hormone production.
flourish and accounts for her recurrent episodes of thrush. Endocrineweb. 2018. https://www.endocrineweb.com/conditions/
hypoparathyroidism/hypoparathyroidism (accessed 9 March 2022)
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Caron P, Brue T, Raverot G et al. Signs and symptoms of acromegaly at diagnosis: 2022)

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