The document discusses Adrenocorticotropic Hormone (ACTH), including its production, regulation, normal levels, and associated abnormalities such as Cushing's syndrome, Nelson syndrome, and Addison's disease. It provides insights into symptoms, treatment options, and the significance of ACTH testing in diagnosing related endocrine disorders. Furthermore, it addresses the effect of ACTH levels during pregnancy and the implications of hyper- and hyposecretion.

1. University of Chakwal, Pakistan

2. Topic: Abnormalities of ACTH
Department of Zoology
Presented by: Komal Zahra
Roll no# UOC-BSZOL-F2020/035
BS Zoology
Session: 2020-2024
Subject: Endocrinology
Instructor Name: Dr. Syeda Nadia Ahmad

3. ACTH :
ACTH is a polypeptide tropic hormone.
 Produced by the pituitary gland in the brain.
Composed of 39 Amino acid.
It has a molecular weight of 4540 Da.
 Stimulate the adrenal glands to produce and
release cortisol into the bloodstream.
(Cuijpers P.,2019).
Figure #1: ACTH
https://images.app.goo.gl/EzMF
gFmSbeSG8NuL8

4. Regulation of ACTH:
ACTH (adrenocorticotropic hormone) is controlled by the
hypothalamus-pituitary-adrenal (HPA) axis.
 The hypothalamus releases corticotropin-releasing hormone
(CRH),
 which signals the pituitary gland to produce and release ACTH.
 ACTH then stimulates the release of CRH and ACTH is
regulated by a feedback loop.
When cortisol levels are high, they inhibit the release of CRH
and ACTH, helping to maintain a balance in the body’s stress
response(Caldwell H.K.,2018).

5. Regulation of ACTH :
 Conversely, when cortisol
levels are low, the
hypothalamus and pituitary
release more CRH and
ACTH to stimulate cortisol
production.
The adrenal glands to
produce and release
cortisol(Caldwell
H.K.,2018).
Figure #2: HPA axis
https://images.app.goo.gl/Zn8KCRqu
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6. Normal Range:
Like cortisol, the level of ACTH in your blood normally peaks
in the early morning and declines throughout the day, reaching
its lowest level around midnight.
Normal ACTH levels in the blood are generally between 9 and
52 picograms per milliliter (pg/mL)(Kirsch P.,2017).

7. Hyper-secretions of ACTH:
High ACTH levels are often associated with increased
cortisol productions.
Hyper-secretions of ACTH results:
Cushing’s Disease/syndrome
Nelson Syndrome
Ectopic ACTH tumor Production(Hiroi, N.,etal.2020)

8. Cushing Syndrome :
Cushing’s syndrome is a condition
characterized by prolonged
exposure to high levels of ACTH.
A benign (non-cancerous) tumor
(adenoma) in your pituitary gland
that produces excess amounts of
ACTH, which then elevates
cortisol levels(Cid-
joffre,etal.,2020).
Figure #3: Cushing syndrome
https://images.app.goo.gl/1tcM4Zx
GwTjTTg6N7

9. Cushing Syndrome:
Symptoms of Cushing’s Syndrome:
Weight Gain
 Skin Changes
Muscle Weakness
High Blood Pressure
Glucose Intolerance
Irregular Menstrual Periods
Emotional Changes
Increased thirst and urination.

10. Treatment :
Treatment involves surgery to remove the pituitary tumor, if
possible.
 After surgery, the pituitary gland may slowly start to work
again and return to normal.
Radiation treatment of the pituitary gland may also be used if
the tumor is not completely removed.
Medication (Carter,etal.2019).

11. Ectopic ACTH Tumor:
An ectopic ACTH tumor refers to a tumor outside the pituitary
gland
 That produces high level of adrenocorticotropic hormone
(ACTH).
This can lead to increased cortisol production.
It is rare, and between 10% and 20% of Cushing’s syndrome (CS)
could be found associated with an ectopic tumor.
Symptoms same like Cushing’s syndrome
Tumors that can produce ACTH include:

12. Ectopic ACTH tumor:
Benign carcinoid tumors of the lung,
Islet cell tumors of the pancreas,
Medullary carcinoma of the thyroid,
 Small cell tumors of the lungs
 And tumors of the thymus gland
Treatment include:
Surgery, Chemotherapy, Radiation Therapy, Medications
and supportive care(Liddle, G. W.etal,2017).

13. Nelson syndrome:
Enlarging tumor in the pituitary gland,
 named after the endocrinologist Don Nelson who described
the condition in 1958.
The tumor produces an excess of a hormone called ACTH
hormone, which is involved in the production of other steroid
hormones (such as cortisol).
Large tumors invade areas around the pituitary gland, which
may cause a reduction in levels of other hormones.
The enlarged tumor compresses the rest of the pituitary
gland(Cable & Grider,.2020).

14. The tumour can also grow upwards
from the pituitary gland and compress
vital nerves involved in vision.
Symptoms of Nelson Syndrome:
Hyperpigmentation
Visual Disturbances
Headaches
Fatigue and Weakness
Treatment Options:
Surgery, Radiation Therapy,
Medication and Regular Monitoring.
Figure #4 : Pituitary Tumor
https://images.app.goo.gl/zXfcz
n4CTYp8Bh499

15. High level of ACTH in pregnancy:
The high secretion of ACTH at the beginning of the last
trimester of pregnancy may stimulate the development of the
adrenal cortex
 And result in the increased cortisol secretion necessary for
fetal lung maturation.
Placental CRH stimulates the production of maternal
adrenocorticotropin hormone (ACTH) and cortisol,
leading to substantial increases in maternal serum cortisol
levels during the third trimester.

16. Hypo-secretion of ACTH:
Hyposecretion in which low level of ACTH production.
The diseases include:
Hypopituitarism
Addison Disease

17. Hypopituitarism:
This is a rare condition in which there’s a lack (deficiency) of one,
multiple or all of the hormones made by your pituitary gland.
 ACTH can be one of the affected hormones.
Any type of damage to your pituitary gland, such as pressure on the
gland, surgical damage or radiation therapy, can cause
hypopituitarism.
Hypopituitarism can affect anyone at any age.
There are approximately 10 to 40 new cases per one million people
a year(Cassata,.2021).

18. Symptoms:
Fatigue, Weight loss or gain, Changes
in appetite and metabolism, Weakness
especially in muscles, Decreased
libido, Irregular or absent menstrual
periodsin In women, Infertility,
Sensitivity to cold or difficulty staying
warm, Affecting thyroid hormone
levels, Low blood pressure, Joint pain
and Headaches.
Treatment:
Some hormone replacement therapies,
Figure #5: Hypopituitarism
https://images.app.goo.gl/dH3BYDG
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19. Addison Disease:
Addison Disease occur due to low
level of ACTH.
Symptoms of Addison’s Disease:
Fatigue, Weight loss, Low Blood
pressure, Skin changes and
Hyperpigmentation.
Treatment:
Hormone replacement therapy
with glucocorticoids, such as
hydrocortisone(Ray,.2019). Figure #6: Addison ‘s disease
https://images.app.goo.gl/UpMfS
gXAEahRrucW9

20. ACTH Test:
The ACTH test measures
adrenocorticotropic hormone
levels in the blood.
ACTH Test Procedure:
 The ACTH test typically involves
drawing blood, usually in the
morning when cortisol levels peak
and then blood samples are taken
to observe the adrenal gland’s
response.
Figure #7: ACTH test
https://images.app.goo.gl/vkRKqM
tk9e34Edq67

21. Results Interpretation:
Normal Results:
 Adequate cortisol production after ACTH stimulation
Low ACTH Levels:
Possible adrenal insufficiency or Addison’s disease.
High ACTH Levels:
Suggestive of conditions like Cushing’s syndrome,or a
pituitary gland issue(May, M. E.,etal.2019).

22. References:
Hiroi, N., Yakushiji, F., Shimojo, M., Watanabe, S., Sugano, S.,
Yamaguchi, N., & Miyachi, Y. (2020). Human ACTH
hypersensitivity syndrome associated with abnormalities of the
ACTH receptor gene. Clinical Endocrinology, 48(2), 129-134.
May, M. E., & Carey, R. M. (2019). Rapid adrenocorticotropic
hormone test in practice. Retrospective review. The American
journal of medicine, 79(6), 679-684.
Liddle, G. W., Givens, J. R., Nicholson, W. E., & Island, D. P.
(2017). The ectopic ACTH syndrome. Cancer Research,
25(7_Part_1), 1057-1061.