Incomplete Diagnosis Without the Endocrine System: A Broader Look at Hormonal and Metabolic Disorders in All Genders

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Since 1997, I’ve been puzzled by the consistent neglect of the endocrine system—particularly hormones—in standard medical testing. Despite its central role in maintaining metabolic balance, hormonal regulation is often treated as secondary or peripheral, especially outside of overt reproductive concerns. In conditions like Polycystic Ovary Syndrome (PCOS), the focus has traditionally been on reproductive symptoms, reinforcing a narrow view of endocrine disorders as primarily affecting women’s fertility.

This limited perspective not only overlooks the systemic nature of hormonal regulation but also contributes to incomplete and delayed diagnoses in both women and men. The endocrine system governs critical functions such as metabolism, glucose regulation, stress response, and energy management. When this system is not fully assessed, key hormonal imbalances—like insulin resistance, thyroid dysfunction, or adrenal stress—are often missed.

Hormonal dysfunction may present differently across sexes, yet many of the underlying metabolic pathways are shared. Without a comprehensive approach to endocrine evaluation, healthcare providers risk treating isolated symptoms while leaving the root causes unaddressed—regardless of the patient's gender.

Beyond Reproduction: The Endocrine System’s Central Role in Health

The endocrine system regulates the body through hormones that impact nearly every organ. Key glands—including the pancreas, thyroid, adrenal glands, and the hypothalamic-pituitary axis—work together to maintain homeostasis. When one system is disrupted, others often compensate or fail, creating complex symptom patterns that can be misunderstood or misattributed.

Ignoring these interactions in diagnostic protocols leads to incomplete clinical pictures, especially in conditions like PCOS in women or hypogonadism and metabolic syndrome in men. Both may present with fatigue, weight changes, mood disturbances, and insulin resistance—symptoms that can be mistakenly treated in isolation if the endocrine foundation is not evaluated.

Summary Table: Examples of Endocrine Disorders

Disorder

Primary Gland

Hormone(s) Affected

Common Symptoms

Cushing’s Syndrome

Adrenal

Cortisol

Obesity, muscle loss, high BP

Addison’s Disease

Adrenal

Cortisol, Aldosterone

Fatigue, low BP, weight loss

Hypothyroidism

Thyroid

T₃, T₄

Weight gain, depression, cold intolerance

Hyperthyroidism

Thyroid

T₃, T₄

Weight loss, anxiety, palpitations

PCOS

Ovaries/Adrenals

Androgens, Insulin

Irregular cycles, acne, insulin resistance

Male Hypogonadism

Testes/Pituitary

Testosterone

Low libido, fatigue, infertility

Type 2 Diabetes

Pancreas

Insulin

High blood sugar, fatigue, obesity

Prolactinoma

Pituitary

Prolactin

Galactorrhea, amenorrhea, sexual dysfunction

  

Core Endocrine Systems Impacting Metabolic Health

A more complete understanding of metabolic disorders in all genders requires attention to these hormonal systems:

Pancreas: Insulin and Glucagon

  • Insulin lowers blood glucose by promoting uptake and storage (glycogen, fat).

  • Glucagon raises glucose levels by promoting glycogen breakdown and gluconeogenesis.

  • Dysregulation leads to insulin resistance, a core feature of metabolic syndrome, PCOS, and Type 2 diabetes in both sexes.

Thyroid Gland: T₃ and T₄

  • Controls basal metabolic rate, body temperature, oxygen use, and protein synthesis.

  • Hypothyroidism can cause fatigue, weight gain, and menstrual irregularities in women, and decreased libido, depression, or cognitive issues in men.

Adrenal Glands: Cortisol and Adrenaline

  • Cortisol manages long-term stress and raises blood glucose during fasting.

  • Adrenaline promotes rapid energy release and increased heart rate.

  • Chronic stress or adrenal dysfunction can lead to metabolic exhaustion, abdominal weight gain, and insulin resistance.

Hypothalamic-Pituitary Axis

  • Governs thyroid (HPT axis), adrenal (HPA axis), and gonadal (HPG axis) hormone production.

  • Pituitary dysfunction can lead to low testosterone in men or menstrual irregularities in women, as well as systemic metabolic disruption.

Adipose Tissue: Leptin

  • Regulates hunger and energy expenditure by signaling long-term energy stores.

  • Leptin resistance, common in obesity, leads to poor appetite regulation and metabolic imbalance.

Bone: Osteocalcin

  • Emerging evidence suggests bone-derived hormones influence insulin sensitivity and energy metabolism in both men and women.

Gender-Inclusive Endocrine Dysfunction: Shared and Unique Features

In Women (e.g., PCOS):

  • Irregular periods, hirsutism, acne, and infertility may dominate.

  • Underlying metabolic signs like insulin resistance, NAFLD, and hypothyroidism are often missed when diagnosis focuses only on reproductive symptoms.

In Men (e.g., Metabolic Hypogonadism):

  • Fatigue, low libido, decreased muscle mass, and mood changes may occur.

  • Often linked to low testosterone, insulin resistance, or undiagnosed thyroid or adrenal issues.

Both sexes can suffer from undiagnosed endocrine imbalances that lead to chronic disease if not identified and managed early.

Critical Gaps in Standard Testing

In both men and women, current diagnostic approaches often overlook the systemic nature of hormonal disorders. Key gaps include:

1. Inadequate Screening for Insulin Resistance

  • Rarely tested in early evaluations, despite its central role in PCOS and male hypogonadism.

  • Simple tests like fasting insulin, HOMA-IR, and oral glucose tolerance test (OGTT) are underutilized.

2. Limited Androgen Assessment

  • In women, mild or adrenal-driven hyperandrogenism may go undetected.

  • In men, testosterone is often measured without evaluating free testosterone, SHBG, or the role of cortisol and thyroid dysfunction in suppressing testosterone production.

3. Thyroid Testing Gaps

  • Subclinical hypothyroidism is common and often missed with TSH alone.

  • Free T3, Free T4, and thyroid antibodies provide a more complete picture.

4. Overlooking Adrenal Stress

  • Cortisol testing (serum, saliva, urine) is rarely ordered unless Cushing’s or Addison’s is suspected, despite its role in metabolic disorders.

  • Chronic low or high cortisol contributes to insulin resistance, fatigue, and altered body composition.

5. Cardiometabolic Risk Ignored in Early Diagnosis

  • Lipid panels, liver enzymes (for NAFLD), and blood pressure monitoring are essential but often omitted from endocrine evaluations.

Comprehensive Endocrine-Metabolic Testing

To achieve accurate diagnosis across sexes, clinicians should incorporate the following evaluations:

Glucose and Insulin Regulation

  • Fasting Blood Glucose

  • HbA1c

  • Fasting Insulin and Glucose Ratio / HOMA-IR

  • OGTT (especially in overweight/obese individuals)

Thyroid Function

  • TSH

  • Free T4 and Free T3

  • Thyroid Antibodies (TPOAb, TgAb)

Adrenal Function

  • Serum Cortisol (morning)

  • Salivary Cortisol (diurnal pattern)

  • 24-hour Urine Cortisol

  • ACTH Stimulation Test

  • DHEAS (for androgen source analysis)

Sex Hormones

  • Total and Free Testosterone

  • Sex Hormone-Binding Globulin (SHBG)

  • LH and FSH

  • Estradiol (in men and women where indicated)

  • Prolactin (especially when low libido or menstrual irregularities are present)

Growth and Metabolic Hormones

  • IGF-1 and Growth Hormone

  • Leptin (if obesity or suspected leptin resistance)

Dynamic Tests and Imaging

  • Insulin Tolerance Test (for HPA axis evaluation)

  • TRH or GnRH stimulation tests

  • Pituitary or adrenal imaging if structural causes are suspected

A More Complete Approach: Inclusive and Systemic

The endocrine system does not function in isolation, nor should diagnosis. A male presenting with fatigue and low libido may have low testosterone—but why? Could the root be insulin resistance, thyroid dysfunction, or chronic stress suppressing the hypothalamic-pituitary-gonadal axis? Similarly, a female with irregular cycles might not just have ovarian dysfunction, but also underlying hypothyroidism or undiagnosed adrenal stress.

By extending diagnostic evaluations to the full endocrine-metabolic system, clinicians can:

  • Address root causes, not just symptoms

  • Detect early metabolic dysfunctions before they progress to chronic disease

  • Tailor treatments to individual hormonal profiles

  • Improve outcomes in both reproductive and general health

Conclusion

A narrow diagnostic lens that focuses on sex-specific symptoms or isolated lab markers often misses the complex, interconnected dysfunctions of the endocrine system. Whether it's PCOS in women or metabolic hypogonadism in men, failing to evaluate the broader hormonal environment leads to incomplete diagnosis, delayed treatment, and worsening outcomes.

To move forward, we must adopt gender-inclusive, system-wide endocrine assessments that reflect the reality of hormonal health. The endocrine system affects everyone—and it must be central to any meaningful approach to diagnosis and care.

References:

PCOS and Endocrine-Metabolic Dysfunction

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome†
https://academic.oup.com/humrep/article/33/9/1602/5056069?login=false

Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
https://academic.oup.com/edrv/article-abstract/18/6/774/2530788?redirectedFrom=fulltext&login=false

Metabolic Syndrome and Hormonal Disorders in Men

Testosterone: a metabolic hormone in health and disease
https://joe.bioscientifica.com/view/journals/joe/217/3/R25.xml

Low Testosterone in Men with Type 2 Diabetes: Significance and Treatment
https://academic.oup.com/jcem/article-abstract/96/8/2341/2834088?redirectedFrom=fulltext&login=false

Thyroid and Adrenal Function in Metabolic Health

Hypothyroidism
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30703-1/abstract

Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline https://academic.oup.com/jcem/article/101/2/364/2810222?login=false

Hormonal Regulation and Metabolism

Insulin signalling and the regulation of glucose and lipid metabolism
https://www.nature.com/articles/414799a

Thyroid Hormone Regulation of Metabolism https://journals.physiology.org/doi/full/10.1152/physrev.00030.2013

Adipose Tissue as an Endocrine Organ
https://academic.oup.com/jcem/article-abstract/89/6/2548/2870285?redirectedFrom=fulltext&login=false

Emerging Research on Bone and Metabolism

Developmental pathways activated in melanocytes and melanoma https://www.sciencedirect.com/science/article/abs/pii/S0003986114002744?via%3Dihub

General Endocrine Testing Guidelines

Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association
https://www.endocrinepractice.org/article/S1530-891X(20)43030-7/fulltext

Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance
https://academic.oup.com/edrv/article/39/5/803/5052770?login=false

© 2000-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9 

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